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1.
Phytomedicine ; 63: 153058, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394414

RESUMO

BACKGROUND: Sulforaphane (SFN), a natural compound present in cruciferous vegetable, has been shown to possess anti-cancer activities. Cancer stem cell (CSC) in bulk tumor is generally considered as treatment resistant cell and involved in cancer recurrence. The effects of SFN on nasopharyngeal carcinoma (NPC) CSCs have not yet been explored. PURPOSE: The present study aims to examine the anti-tumor activities of SFN on NPC cells with CSC-like properties and the underlying mechanisms. METHODS: NPC cells growing in monolayer culture, CSCs-enriched NPC tumor spheres, and also the NPC nude mice xenograft were used to study the anti-tumor activities of SFN on NPC. The population of cells expressing CSC-associated markers was evaluated using flow cytometry and aldehyde dehydrogenase (ALDH) activity assay. The effect of DNA methyltransferase 1 (DNMT1) on the growth of NPC cells was analyzed by using small interfering RNA (siRNA)-mediated silencing method. RESULTS: SFN was found to inhibit the formation of CSC-enriched NPC tumor spheres and reduce the population of cells with CSC-associated properties (SRY (Sex determining Region Y)-box 2 (SOX2) and ALDH). In the functional study, SFN was found to restore the expression of Wnt inhibitory factor 1 (WIF1) and the effect was accompanied with the downregulation of DNMT1. The functional activities of WIF1 and DNMT1 were confirmed using exogenously added recombinant WIF1 and siRNA knockdown of DNMT1. Moreover, SFN was found to inhibit the in vivo growth of C666-1 cells and enhance the anti-tumor effects of cisplatin. CONCLUSION: Taken together, we demonstrated that SFN could suppress the growth of NPC cells via the DNMT1/WIF1 axis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos Fitogênicos/farmacologia , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Isotiocianatos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Brassicaceae/química , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , DNA (Citosina-5-)-Metiltransferase 1/genética , Humanos , Isotiocianatos/administração & dosagem , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Cell Biochem Funct ; 37(7): 486-493, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368181

RESUMO

Although the spontaneous chloride currents (SCC) have been well studied in the normal cells, its properties and roles in neoplasms cells are still unknown. Here, we found that the SCC was manifested in the poorly differentiated human nasopharyngeal carcinoma CNE-2Z cells, with some differences such as lower occurrence and bigger current density than those of the volume-activated chloride currents (VACC). NPPB, a chloride channel blocker, inhibited the SCC much stronger than the VACC. Down-regulation of chloride channel -3 (ClC-3), a volume and mechanically dependent ion channel, could significantly decrease the VACC, but not in SCC. The occurrence, latency, and mean density of the SCC were much lower in the normal nasopharyngeal NP69-SV40T cells than those in CNE-2Z cells. Our results demonstrated that the spontaneous electrical reactivity of neoplasm cells is higher than that of normal cells, which probably relates to their high physiological activity of neoplasm cells. SIGNIFICANCE OF THE STUDY: Spontaneous chloride currents (SCC) are well known in excitable tissues and regulate a variety of physiological and pathophysiological processes. During our researching on the volume-activated chloride currents (VACC) in human nasopharyngeal carcinoma CNE-2Z cells, SCC could be also observed with different properties from VACC. Meanwhile, the occurrence, latency, and mean density of the SCC were much higher in CNE-2Z cells than those in normal nasopharyngeal NP69-SV40T cells. Our results revealed the expression and characteristics of SCC in carcinoma cells and provided a preliminary experimental basis for further exploring the function of SCC in tumour cell biology.


Assuntos
Cloretos/metabolismo , Células Epiteliais/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Células Cultivadas , Humanos
3.
Medicine (Baltimore) ; 98(28): e16327, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305420

RESUMO

For patients with nasopharyngeal carcinoma (NPC), prognostic indicators to customize subsequent biologically conformal radiation therapy may be obtained via 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT). This retrospective study assessed the prognostic significance and feasibility of conformal radiotherapy for NPC, based on F-FDG PET/CT. Eighty-two patients with NPC underwent F-FDG PET/CT prior to intensity-modulated radiation therapy (IMRT). The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the primary tumor were measured, with MTVx based on absolute SUVx values ≥ specific threshold x on each axial image. The cut-off SUVmax and MTV values for predicting 3-year progression-free survival (PFS) were calculated according to a receiver operating characteristic curve. Assessed were correlations between SUVmax and MTV and between threshold x and MTVx, and the MTV percentage of the primary tumor volume at threshold x. The SUVmax and MTV were positively associated, as were MTV and primary tumor volume. Primary tumor volume, SUVmax, and MTV were significant predictors of survival. The 3-year PFS rates for SUVmax ≤8.20 and >8.20 were 91.1% and 73.0%, respectively (P = .027). With furthermore analysis, patients having tumor with smaller MTV had higher 3-year PFS than patients having tumor with larger MTV. The 3-year PFS rate was inversely related to MTV. SUVmax and MTV, derived by PET/CT, are important for assessing prognosis and planning radiotherapy for patients with NPC. Small MTV indicated better 3-year PFS compared with large MTV. For the best therapeutic effect, MTV4.0 was the best subvolume to determine radiotherapy boost.


Assuntos
Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radioterapia Conformacional , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Análise de Sobrevida , Carga Tumoral , Adulto Jovem
4.
Asian Pac J Cancer Prev ; 20(7): 2125-2130, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350975

RESUMO

Background: Nasopharyngeal carcinoma (NPC) is a malignancy with high incidence in Southern China and South-East Asia. NPC incidence among males in Indonesia is estimated around 8.3/100,000 populations. Tobacco smoking is a common risk factor for cancer, including NPC. P16 is one of the key proteins related to the activation of apoptotic pathways, that commonly change during carcinogenesis. Carcinogenesis is often related to environmental exposure, including tobacco smoke. Objective: To analyze the association between P16 protein and smoking status among NPC subjects in Indonesia. Methods: Forty formalin fixed-paraffin embedded NPC tissue samples of known smoking status (20 smokers, 20 non-smokers) were collected from the Department of Anatomical Pathology, Dr. Sardjito Hospital, Yogyakarta. P16 was detected by immunohistochemistry staining. German semi-quantitative scoring system was applied to the P16 staining. Expression index with the score of 0 to 3 was classified as negative staining, meanwhile 4 to 12 was classified as positive staining. The association between P16 (score) and smoking status among NPC patients was analyzed using Fischer exact test. One-sided p ≤ 0.05 was considered as statistically significant. Results: All samples were Javanese males, with age range 25-76 years old. P16 positive staining among smokers was 5% (1/20), while among non-smokers was 40% (8/20). P16 among smokers was significantly lower than non-smokers patients (p=0.010). No difference was found between quantity of smoke and P16 score. Conclusion : A significant association between P16 and smoking status in Indonesian NPC patients has been revealed. The result of this study may be used to improve prevention and management of NPC cases related to smoking habit in Indonesia.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Nasofaríngeas/etiologia , Fumar/epidemiologia , Fumar/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Prognóstico , Fumar/efeitos adversos
5.
Gene ; 715: 144017, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31357026

RESUMO

SRY-related high-mobility-group box 9 (SOX9) is a member of the SOX family of transcription factors. Accumulating evidence has shown that SOX9 plays a significant role in various malignancies. However, the role of SOX9 in nasopharyngeal carcinoma (NPC) remains unknown. In the present study, up-regulation of SOX9 was observed in both NPC tissues and different NPC cells. Overexpression of SOX9 promoted NPC cell proliferation, migration and invasion. Conversely, knock down of SOX9 inhibited NPC proliferation, colony formation, migration and invasion. Mechanistically, SOX9 bound directly to the promoter region of BMP2 and increased BMP2 expression. In addition, overexpression of SOX9 activated the mTOR pathway partly through BMP2. Collectively, these results identify a novel role for SOX9 as a potential therapeutic marker for the prevention and treatment of NPC.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Movimento Celular , Proliferação de Células , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição SOX9/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Morfogenética Óssea 2/genética , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Fatores de Transcrição SOX9/genética , Serina-Treonina Quinases TOR/genética
6.
Gene ; 710: 103-113, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31158447

RESUMO

Epithelial-mesenchymal transition (EMT) symbolizes the predominant program of advanced-stage cancer, it is critical in cancer progression, metastasis, and chemotherapy resistance. In this study, the metastatic properties of nasopharyngeal carcinoma (NPC) cells were evaluated by morphological examination, wound healing assay, migration and invasion assay. Western blotting and qRT-PCR were used to ascertain the expression of markers which were associated with EMT. The effects of miR-205-5p on invasion, migration, EMT and proliferation of NPC cells were evaluated and the molecular mechanisms of their interaction were explored. In this study, we manifested firstly that the expression of miR-205-5p in cisplatin-resistant NPC cell line HNE1/DDP was obviously up-regulated than that in its parental cell line HNE1. Then we analyzed the specific role of miR-205-5p through functional assays by transfecting specific mimics and inhibitors. The results indicated that low expression of miR-205-5p restrained EMT progression of HNE1/DDP cells. Further studies on the mechanism of miR-205-5p manifested that PTEN was a downstream candidate gene of miR-205-5p, down-regulated PTEN expression could counteract the effect of miR-205-5p inhibitors, and the regulation of EMT by miR-205-5p on HNE1/DDP cells depended on the PI3K/AKT signaling pathway. Overall, our results indicated that miR-205-5p was targeting PTEN to regulate EMT through the PI3K/AKT pathway. This study will supply a new treatment target for advanced NPC.


Assuntos
Resistencia a Medicamentos Antineoplásicos , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , PTEN Fosfo-Hidrolase/genética , Regulação para Cima , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisplatino , Progressão da Doença , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Mol Pharmacol ; 96(2): 168-179, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31175180

RESUMO

Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investigation. In this study, we identified a previously unrecognized role of HSP90 in cooperating with signal transducer and activator of transcription 3 (STAT3) to regulate TWIST1 transcription in cancer cells. The HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin suppressed TWIST1 mRNA expression and promoter activity in epithelial ovarian cancer, renal clear cell cancer, and nasopharyngeal cancer cell lines. The interactions between HSP90 and transcription factors were visualized in cancer cell lines and tumor tissues using proximity ligation assays. Our findings reveal that HSP90 promotes the binding of STAT3 to the TWIST1 promoter, leading to the transcription of TWIST1. The inhibition of HSP90 downregulates STAT3 activity and TWIST1 transcription, thereby suppressing EMT and potentially inhibiting tumor progression, metastasis, and chemoresistance in different types of cancers. SIGNIFICANCE STATEMENT: Our study provides new evidence that HSP90 promotes EMT through enhancing TWIST1 transcription, which can be suppressed by HSP90 inhibitors. The HSP90 inhibitor inhibits EMT, thus potentially slowing down tumor growth, invasion, dissemination, metastasis, and drug resistance. These findings will hopefully pave the way for new therapeutic opportunities to target EMT and metastasis using HSP90 inhibitors.


Assuntos
Benzoquinonas/farmacologia , Neoplasias Renais/genética , Lactamas Macrocíclicas/farmacologia , Neoplasias Nasofaríngeas/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Fator de Transcrição STAT3/metabolismo , Proteína 1 Relacionada a Twist/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , Análise Serial de Tecidos , Transcrição Genética/efeitos dos fármacos
8.
Ann Otol Rhinol Laryngol ; 128(11): 1061-1072, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31148463

RESUMO

OBJECTIVE: Juvenile nasopharyngeal angiofibroma (JNA) is a rare vascular tumor of unknown etiology. Studies investigating the molecular and genetic determinants of JNA are limited by small sample size and inconsistent approaches. The purpose of this study is to examine all eligible JNA studies in aggregate, applying qualitative analysis to highlight areas of particular relevance, including potential targets for therapeutic intervention. METHODS: The PubMed, MEDLINE, Embase, Web of Science, Cochrane, and CINAHL databases were screened with inclusion and exclusion criteria applied to all citations. Manuscripts investigating the genetic determinants, histopathogenesis, and heritability of juvenile nasopharyngeal angiofibroma were included. Non-English studies, case reports, and articles focusing on clinical management without original data were excluded. Full text articles were obtained. A qualitative synthesis of data was performed. RESULTS: A total of 59 articles met criteria for inclusion. These were divided into 6 categories based on the primary topic or target discussed, (1) steroid hormone receptors, (2) chromosomal abnormalities, (3) growth factors, (4) genetic targets, (5) molecular targets, (6) Wnt cell signaling, and (7) studies that overlapped multiple of the aforementioned categories. Although relatively low n values prevent definitive conclusions to be drawn, a predominance of certain molecular targets such as vascular endothelial growth factor (VEGF) and Wnt/ß-catenin pathway intermediaries is apparent. CONCLUSIONS: Although the etiology of JNA remains elusive, contemporary molecular genetic investigation holds promise for risk stratification and could form the basis of a modernized staging system. A multicenter clinical registry and linked tissue bank would further promote the search for JNA specific biomarkers.


Assuntos
Angiofibroma , Testes Genéticos/métodos , Neoplasias Nasofaríngeas , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas Wnt/genética , Adolescente , Angiofibroma/diagnóstico , Angiofibroma/genética , Angiofibroma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Wnt/metabolismo
9.
Mol Med Rep ; 20(1): 409-416, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180550

RESUMO

Advances in the treatment of nasopharyngeal carcinoma (NPC) have significantly improved the local control rate; however, distant metastasis remains a principal cause of mortality. Previous studies have demonstrated that the expression levels of amyloid ß precursor protein (APP) are increased in NPC. The present study aimed to investigate the association between APP and the development of NPC. In order to knockdown APP expression, an APP­small interfering RNA vector was synthesized and transfected into SUNE­1 cells. Cell Counting Kit­8 assay was performed to assess cell viability. The migratory and invasive abilities of SUNE­1 cells were examined by wound healing and Transwell assays, respectively. Reverse transcription­quantitative polymerase chain reaction and western blotting were performed to measure the mRNA and protein expression levels of APP, and additional factors involved in epithelial­mesenchymal transition (EMT) and in the mitogen­activated protein kinase (MAPK) signaling pathway. APP silencing significantly suppressed cell viability, migration and invasion. In addition, APP interference downregulated the expression levels of metastasis­associated 1, matrix metalloproteinase (MMP)­2 and MMP­9; however, knockdown of APP led to upregulation of tissue inhibitor of metalloproteinases 2 and inhibited EMT. The phosphorylation levels of p38, extracellular signal­-regulated kinases 1/2 and c­Jun N­terminal kinases 1/2 were decreased following downregulation of APP. The present results suggested that APP knockdown may significantly inhibit the development of NPC by suppressing cell viability, migration and invasion, and by inhibiting the EMT process via downregulation of the MAPK signaling pathway. Therefore, APP may facilitate the development of a novel gene therapy for the treatment of NPC.


Assuntos
Precursor de Proteína beta-Amiloide/genética , Transição Epitelial-Mesenquimal , Sistema de Sinalização das MAP Quinases , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Interferência de RNA , RNA Interferente Pequeno/genética
10.
BMC Cancer ; 19(1): 599, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208371

RESUMO

BACKGROUND: Podoplanin (PDPN), a transmembrane O-glycoprotein, is up-regulated in many tumors and is involved in tumor metastasis and malignant progression. In previous studies, we generated a functional blocking monoclonal antibody (mAb, SZ168) against the extracellular domain of human PDPN. This study is aimed to investigate whether blocking PDPN by SZ168 inhibits tumor growth and metastasis. METHODS: Malignant melanoma xenograft model by inoculating subcutaneously human malignant melanoma cell line C8161 into the back of BALB/c nude mice was used. Endogenous PDPN expression in C8161 cells and nasopharyngeal cancer cell line CNE-2 was detected using western blot and flow cytometry. RESULTS: SZ168 significantly inhibited C8161 or CNE-2 cell-induced platelet aggregation in a dose-dependent manner with a maximal inhibition of 73.9 ± 3.0% in C8161 cells or 77.1 ± 2.7% in CNE-2 cells. Moreover, SZ168 inhibited the growth and pulmonary metastasis of C8161cells in vivo. The number of lung metastatic foci in the SZ168-treated group was significantly decreased compared with that in the control mouse IgG group (1.61 ± 0.44 vs.3.83 ± 0.60, P < 0.01). Subcutaneous tumor volume, weight, and incidence were also significantly reduced in the SZ168-treated group compared to the control group (P < 0.05). Additionally, SZ168 recognized PDPN in immunohistochemical analyses of tumor tissue sections. CONCLUSIONS: SZ168 blocks growth and pulmonary metastasis of human malignant melanoma by inhibiting the interaction between tumor PDPN and platelet CLEC-2 and therefore is a promising antibody for therapeutic development against malignant melanoma.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Lectinas Tipo C/metabolismo , Neoplasias Pulmonares/metabolismo , Melanoma/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Animais , Células CHO , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cricetulus , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Agregação Plaquetária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Dis Markers ; 2019: 3857853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236144

RESUMO

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer prevalent in Southern China and Southeast Asia. The current knowledge on the molecular pathogenesis of NPC is still inadequate to improve disease management. Using gene expression microarrays, we have identified the four-jointed box 1 (FJX1) gene to be upregulated in primary NPC tissues relative to nonmalignant tissues. An orthologue of human FJX1, the four-jointed (fj) gene in Drosophila and Fjx1 in mouse, has reported to be associated with cancer progression pathways. However, the exact function of FJX1 in human is not well characterized. The overexpression of FJX1 mRNA was validated in primary NPC tissue samples, and the level of FJX1 protein was significantly higher in a subset of NPC tissues (42%) compared to the normal epithelium, where no expression of FJX1 was observed (p = 0.01). FJX1 is also found to be overexpressed in microarray datasets and TCGA datasets of other cancers including head and neck cancer, colorectal, and ovarian cancer. Both siRNA knockdown and overexpression experiments in NPC cell lines showed that FJX1 promotes cell proliferation, anchorage-dependent growth, and cellular invasion. Cyclin D1 and E1 mRNA levels were increased following FJX1 expression indicating that FJX1 enhances proliferation by regulating key proteins governing the cell cycle. Our data suggest that the overexpression of FJX1 contributes to a more aggressive phenotype of NPC cells and further investigations into FJX1 as a potential therapeutic target for NPC are warranted. The evaluation of FJX1 as an immunotherapy target for NPC and other cancers is currently ongoing.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Proteínas de Membrana/genética , Neoplasias Nasofaríngeas/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Proliferação de Células , Ciclinas/genética , Ciclinas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Células HeLa , Humanos , Proteínas de Membrana/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Regulação para Cima
12.
BMC Cancer ; 19(1): 624, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238894

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. METHODS: In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. RESULTS: We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). CONCLUSIONS: TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Receptores Toll-Like/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Criança , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Finlândia , Herpesvirus Humano 4/genética , Papillomavirus Humano 6/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Papillomaviridae/genética , RNA Viral/metabolismo , Taxa de Sobrevida , Glândula Tireoide/metabolismo , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Resultado do Tratamento , Adulto Jovem
13.
BMC Cancer ; 19(1): 503, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138162

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) play a critical role in tumor immune surveillance and immune suppression. Understanding tumor infiltrating T cell subset density, location and PD-1/PD-L1 expression might provide insight for the prediction of tumor therapeutic response and clinical outcome. The purpose of this study was to evaluate the expression and localization of CD8, FoxP3, PD-1, and PD-L1 in primary tumor tissues and their effects on prognosis of stage IV M0 locally advanced nasopharyngeal carcinoma (NPC) patients. METHODS: Sixty NPC patients with stage IV M0 locally advanced disease were treated with definitive chemoradiation. Tumor biopsies from primary lesion were analyzed for the expression and localization of CD8, FoxP3, PD-1, and PD-L1 by immunohistochemistry. Their associations with local disease control and survival of NPC were analyzed. RESULTS: The average follow-up time was 43 months (range from 14 to 61 months). High expression of CD8+, FoxP3+, PD-1+ and PD-L1+ was observed in 60, 86.7, 56.7, and 91.7% of patients, respectively. There was no correlation between clinicopathological features and the expression of these immune markers. High PD-1 expression was found to be associated with lower local disease control (5-year LRFS 23.2% vs 96.8%, p < 0.001) and unfavorable clinical outcome (5-year OS 47.4% vs 73.3%, p = 0.014). In multivariate analysis, PD-1 expression was also an adverse prognostic factor for 5-year OS (HR: 3.68, P = 0.023) and LRFS (HR: 16.89, 1.27-11.84, P = 0.007). Those with PD-1 distribution in both stroma and tumor region had the poorest prognosis. However, PD-1 expression has no significant correlation with 5-year RRFS (p = 0.980) and DMFS (p = 0.865). Patients with both PD-1 and PD-L1 high expression had significant poor local disease control (5-year LRFS 96.0% vs 43.0%, p < 0.001) and overall survival (5-year OS 80.8% vs 45.1%, p < 0.001) compared with the others. Other immune markers were not found having corrections with disease control and survival. CONCLUSIONS: PD-1 high expression, especially with PD-L1 co-expression, is associated with high local recurrence and unfavorable clinical outcome for stage IV M0 NPC patients, and might be a potential target for immunotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Receptor de Morte Celular Programada 1/metabolismo , Regulação para Cima , Adulto , Idoso , Antígenos CD8/metabolismo , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
14.
Int J Mol Med ; 44(1): 57-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115494

RESUMO

Cisplatin is one of the primary compounds used in the treatment of nasopharyngeal carcinoma (NPC), and fibroblast growth factor receptor 2 (FGFR2) has emerged to be a promising target for treatment in various tumors. Therefore, the present study aimed to explore whether the expression levels of FGFR2 in NPC tissues and cell lines were altered, and whether the efficiency of cisplatin was increased following the downregulation of FGFR2. The downregulation of FGFR2 was achieved by transfection with a small interfering RNA against FGFR2. Tissues of patients with NPC were analyzed by immunohistochemistry. Cell viability was examined using a Cell Counting Kit­8 assay. Cell cycle analysis was performed using flow cytometry. mRNA and protein levels were measured by reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. FGFR2 was observed to be overexpressed in cancer tissues of patients with NPC and in the NPC SUNE1, C666­1, 6­10B and HNE­3 cell lines, and resulted in an unfavorable prognosis. Cisplatin treatment decreased cell viability and increased FGFR2 expression. The silencing of FGFR2 was demonstrated to augment the effects of cisplatin treatment, including decreasing the cell viability and inducing cell cycle arrest, which involved the increase and decrease of the durations of G1 and S phases, respectively, and a decrease in the expression levels of cyclin D1 and CDC25A, and increasing the rate of apoptosis via the intrinsic apoptosis pathway, as demonstrated by the upregulation of cleaved caspase­3 and B­cell lymphoma 2 (Bcl­2)­associated X protein and downregulation of Bcl­2, in SUNE1 and C666­1 cell lines. FGFR2 was overexpressed in the cancer tissues of patients with NPC and in NPC cell lines, resulting in an unfavorable prognosis. The downregulation of FGFR2 decreased cell viability via cell cycle arrest at G1 phase, and increased the efficacy of the cisplatin­based induction of apoptosis through the intrinsic apoptosis pathway.


Assuntos
Cisplatino/farmacologia , Regulação para Baixo/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas de Neoplasias/biossíntese , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Fase G1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteínas de Neoplasias/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Fase S/efeitos dos fármacos
15.
Molecules ; 24(10)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108969

RESUMO

Nasopharyngeal carcinoma (NPC) is a high morbidity and mortality cancer with an obvious racial and geographic bias, particularly endemic to Southeast China. Our previous studies demonstrated that Centipeda minima extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from Centipeda minima. In this study, for the first time, we investigated their anti-NPC effects and further explored the related molecular mechanisms. The effects of both arnicolide C and arnicolide D were tested in NPC cells CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. The results showed that the two compounds inhibited NPC cell viability in a concentration- and time-dependent manner. As the inhibitory effect of arnicolide D was the more pronounced of the two, our following studies focused on this compound. Arnicolide D could induce cell cycle arrest at G2/M, and induce cell apoptosis. The molecular mechanism of cell cycle regulation and apoptosis induction was investigated, and the results showed that arnicolide D could downregulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, and upregulate cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by arnicolide D showed dynamic changes according to dose and time. Taken together, arnicolide D modulated the cell cycle, activated the caspase signaling pathway, and inhibited the PI3K/AKT/mTOR and STAT3 signaling pathways. These findings provide a solid base of evidence for arnicolide D as a lead compound for further development, and act as proof for the viability of drug development from traditional Chinese medicines.


Assuntos
Asteraceae/química , Lactonas/farmacologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Sesquiterpenos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
16.
PLoS One ; 14(4): e0215299, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973923

RESUMO

Steroid receptor coactivator 1 (Src-1) and Twist1 are aberrantly upregulated in a variety of tumors and play an important role in tumor progression. However, the exact role of Src-1 and Twist1 in nasopharyngeal carcinoma (NPC) is uncertain. In this study, we investigated the possible prognostic value and biological effect of Src-1 and Twist1 in NPC. Src-1 and Twist1 expression was detected in a cohort of NPC patients (n = 134) by qRT-PCR. Kaplan-Meier survival analysis was used comparing overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional hazard regression model. Biologic effect of Src-1 and Twist1 in NPC cell lines was evaluated by western blot, colony formation assay, soft agar assay, scratch wound healing assay, transwell invasion assay and tumor xenografts growth. We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and associated with advanced tumor stage, distant metastasis and unfavorable prognosis. Knockdown of Src-1 or Twist1 in human NPC cell line CNE-1 suppressed colony formation, anchorage-independent growth, cell migration, invasion and tumor xenografts growth, while enforced expression of Src-1 or Twist1 in human NPC cell line HNE-2 promotes anchorage-independent growth, cell migration and invasion. In addition, Src-1 and Twist1 could suppress E-cadherin expression and increase Vimentin expression, thus suggested that Src-1 and Twist1 enhanced the malignant behaviors of NPC cells via inducing epithelial-mesenchymal transition (EMT). Our data indicated that Src-1 and Twist1 could be possible prognostic biomarkers and potential therapy targets for patients with NPC.


Assuntos
Transição Epitelial-Mesenquimal/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Proteínas Nucleares/genética , Coativador 1 de Receptor Nuclear/genética , Proteína 1 Relacionada a Twist/genética , Adulto , Idoso , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Feminino , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas Nucleares/metabolismo , Coativador 1 de Receptor Nuclear/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estudos Retrospectivos , Proteína 1 Relacionada a Twist/metabolismo , Regulação para Cima
17.
Chem Biol Interact ; 307: 51-57, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026422

RESUMO

Nasopharyngeal carcinoma (NPC) is a head and neck epithelial malignancy with high prevalence and represents a significant disease burden. Eudesmin is a natural lignin that has been reported to exhibit antitumor effect on lung cancer. However, the effect of eudesmin on NPC has not been investigated. The aim of the present study was to evaluate the role of eudesmin in NPC and to explore the underlying mechanism. The NPC cell lines CNE-1 and HONE-1 were treated with eudesmin for 48 h. Cell viability was measured using MTT assay. Cell apoptosis was detected using flow cytometry. The expression levels of enhancer of zeste homolog 2 (EZH2), Akt, and p-Akt were measured using Western blot analysis. We found that eudesmin inhibited cell viability and induced cell apoptosis of NPC cell lines in a dose-dependent manner. Eudesmin suppressed the expression of EZH2 and blocked the activation of Akt signaling pathway. Inhibition of Akt signaling pathway caused significant decrease in EZH2 expression. Moreover, knockdown of EZH2 attenuated the effects of Akt overexpression on cell viability and apoptosis in NPC cells. In conclusion, eudesmin exhibited antitumor activity via downregulating EZH2 expression through the inhibition of Akt signaling pathway. Eudesmin could be developed as a new pharmacologic approach for NPC treatment.


Assuntos
Antineoplásicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Furanos/farmacologia , Lignanas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Furanos/química , Humanos , Lignanas/química , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Med Sci Monit ; 25: 3161-3169, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31034464

RESUMO

BACKGROUND Radio-resistance is an obstacle to the treatment of human nasopharyngeal carcinoma (NPC). However, how microRNAs (miRNA) are involved in this process remains unclear. In the present study we explored the role and possible molecular mechanism of miR-29a-3p, formerly known as tumor suppressors, in radio-sensitivity of NPC cells. MATERIAL AND METHODS A radio-resistant sub-cell line, CNE-2R, was established to detect the expression of miR-29a/b/c-3p using qRT-PCR. CCK-8 assay, colony formation assay, and single-cell gel electrophoresis (SCGE) assay were carried out to analyze the radio-sensitivity of NPC cells. qRT-PCR, luciferase reporter, and Western blot experiments were performed to validate the targeting of COL1A1 by miR-29a. Short interference RNAs (siRNAs) were used to investigate whether COL1A1 mediates the radio-sensitizer role of miR-29a. Expression of miR-29a and COL1A1 in radio-resistant NPC tissues was finally determined. RESULTS miR-29a was decreased in the radio-resistant CNE-2R cells. Following a time-course irradiation (IR) exposure, miR-29a exhibited a time-dependent decrease. Cellular experiments confirmed that miR-29a induced radio-sensitivity of CNE-2R cells via suppressing cell viability and enhancing cell apoptosis after IR. We confirmed that COL1A1 is a direct target of miR-29a and can exert radio-resistance effects in NPC cells. We also found that knockdown of COL1A1 inhibits NPC cell viability and sensitivity to IR. Finally, we observed a downregulation of miR-29a in radio-resistant NPC tissues and its decrease was associated with upregulation of COL1A1. CONCLUSIONS miR-29a is a critical determinant of NPC radio-response for NPC patients, and its induction provides a promising therapeutic choice to elevate NPC radio-sensitivity.


Assuntos
Regiões 3' não Traduzidas , Colágeno Tipo I/genética , MicroRNAs/biossíntese , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Colágeno Tipo I/metabolismo , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Tolerância a Radiação , Transfecção , Regulação para Cima
19.
Environ Toxicol ; 34(7): 853-860, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30983163

RESUMO

Licochalcone A is widely studied in different fields and possesses antiasthmatic, antibacterial, anti-inflammatory, antioxidative, and anticancer properties. Its antimalignancy activity on renal, liver, lung, and oral cancer has been explored. However, limited studies have been conducted on the inhibitory effects of licochalcone A in human nasopharyngeal carcinoma cells. We determined cell viability using MTT assay. Cell cycle distribution and apoptotic cell death were measured via flow cytometry. Caspase activation and mitogen-activated protein kinase-related proteins in nasopharyngeal cancer cells in response to licochalcone A were identified by Western blot analysis. Results indicated that licochalcone A reduces cell viability and induces apoptosis, as evidenced by the upregulation of caspase-8 and caspase-9, caspase-3 activation, and cleaved-poly ADP-ribose polymerase expression. Treatment with licochalcone A significantly increases ERK1/2, p38, and JNK1/2 activation. Co-administration of a JNK inhibitor (JNK-IN-8) or p38 inhibitor (SB203580) abolishes the activation of caspase-9, caspase-8, and caspase-3 protein expression during licochalcone A treatment. These findings indicate that licochalcone A exerts a cytostatic effect through apoptosis by targeting the JNK/p38 pathway in human nasopharyngeal carcinoma cells. Therefore, licochalcone A is a promising therapeutic agent for the treatment of human nasopharyngeal cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antineoplásicos/farmacologia , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ativação Enzimática/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
20.
Cancer Sci ; 110(6): 2050-2062, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945396

RESUMO

The PPAR coactivator-1α (PGC1α) is an important transcriptional co-activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1α is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1α could sensitize NPC cells to radiotherapy. Mechanically, PGC1α binds to CCAAT/enhancer binding protein ß (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1α/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1α could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1α might improve the therapeutic efficacy of radiotherapy.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Carnitina O-Palmitoiltransferase/genética , Ácidos Graxos/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Estimativa de Kaplan-Meier , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Oxirredução/efeitos da radiação , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos da radiação , Interferência de RNA
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