RESUMO
The present study aimed to investigate the expression levels and clinical value of miR-365 and miR-25 in serum of patients with non-small cell lung cancer (NSCLC). Patients (180) diagnosed with NSCLC at the Affiliated Hospital of Guangdong Medical University from July 2011 to December 2013 were used as the experimental group. Volunteers (90) undergoing health examinations were used as the control group. The serum of the patients was collected after fasting in the morning. The expression levels of miR-365 and miR-25 in the serum of patients was assessed by quantitative real-time PCR (qRT-PCR), and the relationship among miR-365, miR-25 and the postoperative survival rate of NSCLC patients was analyzed. The relative expression level of miR-25 of patients with peripheral infiltration was significantly higher than that of patients without peripheral infiltration (P<0.05). There were significant differences in the relative expression level of miR-25 in different pathological grades and TNM stages, as well as with lymph node metastasis (P<0.05). The survival rate of NSCLC patients with high expression of miR-25 was significantly lower than that of NSCLC patients with low expression of miR-25 (P<0.05). The relative expression level of miR-365 of patients with peripheral infiltration was significantly lower than that of patients without peripheral infiltration (P<0.05). There were significant differences in the relative expression level of miR-365 in different pathological grades and TNM stages, as well as with lymph node metastasis (P<0.05). The survival rate of NSCLC patients with high expression of miR-365 was significantly higher than that of NSCLC patients with low expression of miR-365 (P<0.05). In conclusion, the expression levels of miR-25 and miR-365 were different in the serum of NSCLC patients, and they were closely related to certain clinical characteristics such as peripheral infiltration, pathological grade, tumor diameter, TNM stage and lymph node metastasis. Moreover, it was revealed that miR-25 and miR-365 affected the 5-year survival rate of patients. miR-25 and miR-365 could be used as important tumor markers to evaluate the prognosis of NSCLC patients.
RESUMO
Lung cancer is one of the most common malignancies worldwide, with high mortality and morbidity rates. O2â(2,4âdinitrophenyl)1â[(4ethoxycarbonyl)piperazin1yl]diazen1ium1,2diolate (JSK) is a potent anticancer agent that acts against a subset of human nonsmall cell lung cancer (NSCLC) cell lines; however, the underlying mechanisms of JSK in NSCLC remain unclear. The present study aimed to evaluate the anticancer effect of JSK and investigate its underlying mechanisms in A549 and H460 cells. In the present study, A549 and H460 cells were treated with JSK, and then evaluated by cell viability assay, flow cytometry and western blot analysis. JSK markedly induced cell cycle arrest at the G2/M phase in a concentration and timedependent manner in both cell lines. This was associated with increased expression levels of p53, and the cell cycle inhibitors p21WAF1/CIP1 and p27KIP1, which, in turn, inhibited the expression of Cdc2, cyclin B1 and cyclindependent kinase 2. In addition, JSKinduced inhibition of proliferation was revealed to be partially modulated by the upregulation of p53 and p21WAF1, the ratio of Bax/Bcl2, and the activation of both the intrinsic and extrinsic apoptotic pathways in A549 and H460 cells. These results demonstrated that JSK could trigger cell cycle arrest at the G2/M phase and apoptosis in A549 and H460 cells, which was likely mediated via the p53/p21WAF1/CIP1 and p27KIP1 pathways. Overall, the results indicated that JSK may be used as an anticancer agent for the treatment of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Proteína Supressora de Tumor p53/genética , Células A549 , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Piperazina/análogos & derivados , Piperazina/farmacologiaRESUMO
Tetraspanin 1(TSPAN1) as a clinically relevant gene target in cancer has been studied, but there is no direct in vivo or vitro evidence for pulmonary fibrosis (PF). Using reanalysing Gene Expression Omnibus data, here, we show for the first time that TSPAN1 was markedly down-regulated in lung tissue of patient with idiopathic PF (IPF) and verified the reduced protein expression of TSPAN1 in lung tissue samples of patient with IPF and bleomycin-induced PF mice. The expression of TSPAN1 was decreased and associated with transforming growth factor-ß1 (TGF-ß1 )-induced molecular characteristics of epithelial-to-mesenchymal transition (EMT) in alveolar epithelial cells (AECs). Silencing TSPAN1 promoted cell migration, and the expression of alpha-smooth muscle actin, vimentin and E-cadherin in AECs with TGF-ß1 treatment, while exogenous TSPAN1 has the converse effects. Moreover, silencing TSPAN1 promotes the phosphorylation of Smad2/3 and stabilizes beta-catenin protein, however, overexpressed TSPAN1 impeded TGF-ß1 -induced activation of Smad2/3 and beta-catenin pathway in AECs. Together, our study implicates TSPAN1 as a key regulator in the process of EMT in AECs of IPF.
Assuntos
Transição Epitelial-Mesenquimal/genética , Fibrose Pulmonar Idiopática/genética , Proteína Smad2/genética , Proteína Smad3/genética , Tetraspaninas/genética , beta Catenina/genética , Células A549 , Idoso , Células Epiteliais Alveolares/metabolismo , Animais , Bleomicina , Linhagem Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Tetraspaninas/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , beta Catenina/metabolismoRESUMO
Long noncoding RNAs are capable of regulating gene expression at multiple levels. These RNA molecules are also involved in a variety of physiological and pathological processes. Emerging data demonstrate that a series of differentially expressed long noncoding RNAs are implicated in tumorigenesis. In the present study, we used microarray analysis to identify long noncoding RNAs that are dysregulated in non-small-cell lung cancer when compared to normal lung tissues. Accordingly, we performed quantitative real-time polymerase chain reaction to analyze the levels of long noncoding RNA and the cis target gene. We further found the oncogene property of long noncoding RNA that long noncoding RNA downexpression inhibits non-small-cell lung cancer cells proliferation and migration based on 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and colony formation assays and wound healing as well as transwell assays. The influence of long noncoding RNA on cell cycle of non-small-cell lung cancer cells is also analyzed by flow cytometry. Among the dysregulated long noncoding RNAs, we identified INS-IGF2 readthrough, transcript variant 1, noncoding RNA (NR_003512.3) is upregulated in non-small-cell lung cancer tissues, the cis gene of which is insulin-like growth factor 2 gene hinted by bioinformatics analysis. We also observed that downregulation of INS-IGF2 readthrough, transcript variant 1, noncoding RNA reduces insulin-like growth factor 2 messenger RNA expression. Furthermore, INS-IGF2 readthrough, transcript variant 1, noncoding RNA downregulation suppresses non-small-cell lung cancer cell proliferation and migration. This downregulation results in a concomitant inhibition of the G1/S transition in non-small-cell lung cancer cells. Our findings suggest that INS-IGF2 readthrough, transcript variant 1, noncoding RNA may be an oncogene involved in the development of lung cancer. Therefore, we speculate that INS-IGF2 readthrough, transcript variant 1, noncoding RNA represents a potential therapeutic target for lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Fase G1 , Proteínas Mutantes Quiméricas/genética , RNA Longo não Codificante/genética , Fase S , Apoptose , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Casos e Controles , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Prognóstico , Células Tumorais CultivadasRESUMO
Cathepsin S (CTSS) and Sirtuin-1 (SIRT1) played crucial roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the associations between the polymorphisms of CTSS as well as SIRT1 and COPD in Asian population remain elusive. In the present study, one single nucleotide polymorphism (SNP) in rs12068264 was discovered (in 385 individuals) to be associated with the susceptibility of COPD in a Chinese Han population. The genotyping was performed using improved multiplex ligase detection reaction (iMLDR) technique. Subjects with T allele of rs12068264 in CTSS gene had an increased risk of COPD (T compared with C: odds ratio (OR) = 1.351, 95% confidence interval (95% CI): 1.008-1.811, P=0.044) compared with C allele. Subjects with TT genotype at rs12068264 had a higher risk of COPD in a recessive model (TT compared with TC + CC: OR = 2.30, 95% CI: 1.06-4.989, P=0.035). Compared with the C variant of rs12068264, the homozygous carriers of the TT genotype had higher procalcitonin (PCT) levels. Finally, haplotype analysis demonstrated that the SNPs in the CTSS and SIRT1 gene had no statistical differences between patients with COPD and the controls. In conclusion, the genetic polymorphisms of CTSS were associated with the susceptibility of COPD in a Chinese Han population, which may be helpful in understanding genetic mechanisms underlying the pathogenesis of COPD.
Assuntos
Catepsinas/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , China/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Sirtuína 1/genéticaRESUMO
Nickle (Ni) is a heavy metal found in particulate matter. We previously reported that Ni ions are strongly associated with high apoptosis rates and high expression of IL-1ß in human bronchial epithelial cells following exposure to PM2.5; however, the effects of Ni ions on pulmonary fibrosis have not been fully elucidated. In the current study, we evaluated whether Ni ions can exacerbate bleomycin (BLM)-induced pulmonary fibrosis in a mouse model and illustrated the potential mechanism. Ni ions inhibited cell proliferation and induced apoptosis in A549 and MRC-5 cells. BLM-induced lung injury and fibrosis in mice were significantly enhanced by nickel treatment, and these findings were also supported by inflammatory cell accumulation in bronchoalveolar lavage fluid and elevated levels of pro-inflammatory cytokines in lung tissues. Ni ions also increased extracellular matrix protein levels, including those of type I collagen and MMP9 in mouse lung tissues and cell lines. Moreover, Ni ions promoted the phosphorylation of AKT in this mouse model. The effect of increased collagen levels and MMP9 expression was inhibited by blocking the AKT phosphorylation. Together, these findings suggest AKT activation as a critical contributor to this Ni-exacerbated pulmonary fibrotic process.
Assuntos
Bleomicina/toxicidade , Níquel/toxicidade , Material Particulado/toxicidade , Pneumonia/induzido quimicamente , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/metabolismo , Pneumonia/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44+ CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth, and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro. Surprisingly, the combination with miR-5100 inhibitor significantly decreased the IC50 of LCSCs to cisplatin. Furthermore, miR-5100 increased CSC properties and cisplatin resistance by inhibiting Rab6, a direct target gene of miR-5100. We demonstrated that miR-5100 overexpression increases the cisplatin resistance of the LCSCs through the mitochondrial apoptosis pathway. In conclusion, our results suggest that miR-5100 increases the cisplatin resistance of the LCSCs by inhibiting the Rab6. This study provides novel insight into the regulation of LCSCs by miRNA.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas rab de Ligação ao GTP/genética , Células A549 , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologiaRESUMO
8-Oxoguanine DNA glycosylase (OGG1) is responsible for repairing 8-oxo-7,8-dihydroguanine (8-oxoG). Our previous study demonstrated that α-OGG1 protects cells from oxidative damage-induced apoptosis and mitochondrial dysfunction in human lung cancer cells. However, the function of ß-OGG1 remains to be elucidated. In this study, we demonstrated that overexpressed ß-OGG1 has the same role as α-OGG1 in protecting human bronchial epithelial cells from apoptosis and mitochondrial dysfunction. Furthermore, flow cytometry, confocal microscopy, and western blotting showed that the overexpression of ß-OGG1 could block oxidant-induced apoptosis in human bronchial epithelial cells. Additionally, knocking down OGG1 enhanced oxidative damage-induced apoptosis and mitochondrial dysfunction, whereas the overexpression of ß-OGG1 had the opposite effects and led to the downregulation of Bax and PARP. The antiapoptotic function of ß-OGG1 involved the JNK signaling pathway. These findings suggest that ß-OGG1 and α-OGG1 have a similar function on preventing oxidative damage-mediated apoptosis and mitochondrial dysfunction; these effects might be important in the molecular events underlying oxidant-induced cytotoxicity.
Assuntos
Brônquios/metabolismo , DNA Glicosilases/metabolismo , Sistema de Sinalização das MAP Quinases , Apoptose , Brônquios/citologia , Linhagem Celular , Sobrevivência Celular , Dano ao DNA , DNA Glicosilases/antagonistas & inibidores , DNA Glicosilases/genética , Reparo do DNA , Regulação para Baixo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Regulação para CimaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a devastating disease and the pathogenesis of IPF remains unclear. Our previous study indicated that miR-5100 promotes the proliferation and metastasis of lung epithelial cells. In this study, we investigated the effect and mechanism of miR-5100 on bleomycin (BLM)-induced mouse lung fibrosis and transforming growth factor ß (TGF-ß1) or epidermal growth factor (EGF) induced EMT-model in A549 and Beas-2B cells. The elevated level of miR-5100 was observed in both the mouse lung fibrosis tissues and EMT cell model. Furthermore, the exogenous expression of miR-5100 promoted the EMT-related changes, enhanced TGF-ß1 or EGF-induced EMT and activated the smad2/3 in lung epithelial cells, while silencing miR-5100 had the converse effects. In addition, transwell assay showed that miR-5100 can enhance cell migration. Using target prediction software and luciferase reporter assays, we identified TOB2 as a specific target of miR-5100 and miR-5100 can decrease the accumulation of endogenous TOB2 in A549 and Beas-2B cells. Moreover, the exogenous expression of TOB2 relieves the promotion of miR-5100 on EMT process and migration ability. Taken together, our results indicate that miR-5100 promotes the EMT process by targeting TOB2 associated with activating smad2/3 in lung epithlium cells. Our findings may provide novel insights into the pathogenesis of IPF.
RESUMO
PURPOSE: Accumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: miR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191. RESULTS: miR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion. CONCLUSION: Our findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.
Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , Regiões 3' não Traduzidas , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago , Humanos , Metástase Linfática , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Accumulating evidence demonstrates that a series of differentially expressed lncRNAs is important in tumorigenesis. However, the function of many of the lncRNAs in lung cancer remains elusive. In the present study, we used microarray analysis to identify lncRNAs that are dysregulated in non-small-cell lung cancer (NSCLC) as compared with normal tissues. Among the dysregulated lncRNAs, we identified TFPI2AS1, an antisense transcript of the tumor suppressor TFPI2 (tissue factor pathway inhibitor 2). TFPI2AS1 was shown to be markedly upregulated in NSCLC patient tumors as compared to paired non-tumor samples. TFPI2AS1 knockdown increased NSCLC cell proliferation and migration, which was associated with enhanced G1/S transition and downregulation of cyclin D1 and cyclin-dependent kinases 2 (CDK2), while TFPI2AS1 overexpression had the opposite effect. Knockdown and overexpression experiments also suggested that TFPI2AS1 regulates NSCLC cell migration and AKT activation. Moreover, TFPI2AS1 is a positive regulator of TFPI2. Our findings bring new insights for understanding the role of TFPI2AS1 in mediating the proliferation and migration of NSCLC cells by regulating TFPI2 expression.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Ciclina D1/metabolismo , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular , Glicoproteínas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: This study aimed to explore the effects of HMGA2 on cell proliferation and metastases in lung cancer and its underlying mechanism. METHODS: HMGA2 expression in lung cancer tissues and its association with overall survival were analyzed based on data from a public database. The roles of HMGA2 were validated via loss-of-function and gain-of-function experiments in vitro. HMGA2 regulation by microRNA-195 (miR-195) was validated by real time-PCR, Western blotting, and luciferase reporter assays. RESULTS: HMGA2 was upregulated and associated with reduced overall survival in patients with lung adenocarcinoma. HMGA2 knockdown suppressed the proliferation and motility of H1299 cells, while HMGA2 ectopic expression in A549 cells increased cell proliferation and migration. HMGA2 affected cell apoptosis through caspase 3/9 and Bcl-2, and regulated epithelial-to-mesenchymal transition by targeting Twist 1. Moreover, miR-195 was found to directly target the 3' untranslated region of HMGA2 messenger RNA and suppress its expression in lung cancer. CONCLUSION: This study demonstrated that HMGA2, regulated by miR-195, played important roles in proliferation, metastases, and epithelial-to-mesenchymal transition in lung cancer. HMGA2 might serve as a biomarker and potential therapeutic target for lung cancer treatment.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Regiões 3' não Traduzidas , Células A549 , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metástase Neoplásica , Análise de Sobrevida , Regulação para CimaRESUMO
Although tuberculous pleurisy (TP) presumably involves a hypersensitivity reaction, there is limited evidence indicating overreactive effector responses of γδ T cells and αß T cells and their interrelation with Foxp3(+) Tregs in pleural and other compartments. We found that TP induced reciprocal representations of Foxp3(+) Tregs and Mtb phosphoantigen-specific Vγ2Vδ2 T cells in different anatomic compartments. Patients with TP exhibited appreciable numbers of "proliferating" Ki-67(+) Vγ2Vδ2 T cells in the airway where Foxp3(+) Tregs were not dominant, whereas striking increases in Foxp3(+) Tregs in the blood and pleural compartments coincided with low frequencies of Vγ2Vδ2 T cells. Interestingly, anti-tuberculosis chemotherapy control of Mtb infection in patients with TP reversed reciprocal representations of Foxp3(+) Tregs and proliferating Vγ2Vδ2 T cells. Surprisingly, despite high-level Foxp3(+) Tregs, TP appeared to drive overreactive responses of IFN-γ-producing Vγ2Vδ2, CD4(+)CD25(+), and CD8(+)CD25(+) T effector subpopulations, whereas IL-22-producing Vγ2Vδ2 T cells increased subtly. Th1 effector responses were sustained despite remarkable declines in Foxp3(+) Tregs at 1 mo after the treatment. Overreactive T effector responses of Mtb-reactive γδ T cells, αß CD25(+)CD4(+), and CD25(+)CD8(+) T cell subpopulations appear to be immune features for TP. Increased Foxp3(+) Tregs might be responsive to overreactive TP but unable to influence T effector responses despite having an inverse relation with proliferating Vγ2Vδ2 T cells.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Pleura/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Tuberculose Pleural/imunologia , Adulto , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Pleura/patologia , Tuberculose Pleural/patologia , Interleucina 22RESUMO
FBXO31 is a member of F-box family which is involved in diverse biological functions and development of disease. Recent reports in breast cancer, hepatocellular carcinoma and ovarian cancer demonstrated inhibitory effect of FBXO31 on proliferation and tumorigenesis. However, the function of FBXO31 is not analyzed in lung cancer so far. In this study, we reported that expression of FBXO31 was higher in lung cancer tissues compared with non-cancerous lung tissues, and that higher expression of FBXO31 was significantly associated with tumor size, tumor infiltration, clinical stages and lymph node metastasis. In addition, exogenous expression of FBXO31 promoted cell growth, metastasis and invasion in A549 cells. Conversely, silencing FBXO31 by specific siRNA caused inhibitory effect on cell growth, metastasis and invasion. Moreover, tumorigenicity assays in nude mice showed FBXO31 promoted tumor growth in vivo. In conclusion, our data suggest FBXO31 promotes cell proliferation, metastasis and invasion in lung cancer.
RESUMO
Resveratrol, a nonflavone polyphenol compound, has a chemopreventive and chemotherapeutic effect against the progression of multiple types of cancer, including lung cancer. However, the molecular mechanism underlying the effects of resveratrol on cancer remain to be elucidated. In the present study, using an MTT assay, it was demonstrated that resveratrol inhibited cell proliferation in a concentration and timedependent manner. In addition, morphological features were observed in the A549, human lung cancer cell line, which included cell shrinkage, cells became distorted, certain cells became rounded and there was a concentrationdependent increase in the number of sloughed cells. Cell cycle analysis revealed that resveratrol may induce cell cycle arrest in the G0/G1 phase by downregulating the expression levels of cyclin D1, cyclindependent kinase (CDK)4 and CDK6, and upregulating the expression levels of the CDK inhibitors, p21 and p27. The immunofluorescence and western blot analysis results revealed that resveratrol upregulated the nuclear expression of p53 in A549 cells. Further studies have demonstrated that p53 downregulation did not contribute to the G0/G1 cell cycle arrest induced by resveratrol. In addition, resveratrol had no effect on the expression of p21, through use of the p53 inhibitor, pifithrinα. The present study may offer a scientific basis for the further indepth evaluation of resveratrol in the association of p53 and cell cycle arrest.
Assuntos
Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , ResveratrolRESUMO
OBJECTIVE: To study the effect of triptolide on airway smooth muscle (ASM) proliferation and expressions of c-fos and c-jun in asthmatic rats. METHODS: 70 healthy male sprague-dawley rats were randomly divided into seven groups of 10 each. The asthmatic model was established by ovalbumin inhalation and injection. The mRNA expression of c-fos and c-jun were examined by RT-PCR and their protein expression by immunohistochemical method. The airway wall thickness, the ASM thickness, the number of ASM nucleus and pulmonary tissue changes were observed with microscope. RESULTS: c-fos and c-jun mRNA and protein expressions of asthma groups A and five therapy groups (C, D, E, F and G) were significantly higher than those in the control group B (P < 0.01). The expressions were lower in group C, D, E, F and G than those in group A (P < 0.01). There was no significant difference in the expressions among group C, D, E, F and G (P > 0.05). Triptolide decreased ASM proliferation pathologically in asthmatic rats. CONCLUSIONS: ASM proliferation is a feature of asthma. c-fos and c-jun may promote ASM proliferation in asthma. The remarkable inhibition of ASM proliferation by triptolide was probably due to its inhibitory effect on the expression of c-fos and c-jun.