Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Pharm Sci ; 142: 105100, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31669385

RESUMO

Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.

2.
BMC Cancer ; 19(1): 852, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462229

RESUMO

BACKGROUND: Recently, evidence has emerged that palliative gastrectomy in patients with stage IV gastric cancer may offer some survival benefits. However, the decision whether to perform primary tumor surgery remains challenging for surgeons, and investigations into models that are predictive of prognosis are scarce. Current study aimed to develop and validate prognostic nomograms for patients with metastatic gastric adenocarcinoma treated with palliative gastrectomy. METHODS: The development dataset comprised 1186 patients from the Surveillance, Epidemiology, and End Results Program who were diagnosed with metastatic gastric adenocarcinoma in 2004-2011, while the validation dataset included 407 patients diagnosed in 2012-2015. Variables were incorporated into a Cox proportional hazards model to identify independent risk factors for survival. Both pre- and postoperative nomograms for predicting 1- or 2-year survival probabilities were constructed using the development dataset. The concordance index (c-index) and calibration curves were plotted to determine the accuracy of the nomogram models. Finally, the cut-off value of the calculated total scores based on preoperative nomograms was set and validated by comparing survival with contemporary cases without primary tumor surgery. RESULTS: Age, tumor size, location, grade, T stage, N stage, metastatic site, scope of gastrectomy, number of examined lymph node(s), chemotherapy and radiotherapy were risk factors of survival and were included as variables in the postoperative nomogram; the c-indices of the development and validation datasets were 0.701 (95% confidence interval [CI]: 0.693-0.710) and 0.699 (95% CI: 0.682-0.716), respectively. The preoperative nomogram incorporated age, tumor size, location, grade, depth of invasion, regional lymph node(s) status, and metastatic site. The c-indices for the internal (bootstrap) and external validation sets were 0.629 (95% CI: 0.620-0.639) and 0.607 (95% CI: 0.588-0.626), respectively. Based on the preoperative nomogram, patients with preoperative total score > 28 showed no survival benefit with gastrectomy compared to no primary tumor surgery. CONCLUSIONS: Our survival nomograms for patients with metastatic gastric adenocarcinoma undergoing palliative gastrectomy can assist surgeons in treatment decision-making and prognostication.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Nomogramas , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Cuidados Paliativos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
3.
J Org Chem ; 83(23): 14419-14430, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30383381

RESUMO

An efficient copper-catalyzed radical cascade cyclization strategy was developed, by which a wide variety of 3-sulfonyl substituted indenones were prepared in one pot via reaction of 2-alkynylbenzonitriles with sulfonyl hydrazides in the presence of TBHP and CuI under mild reaction conditions. Much more importantly, the 3-sulfonyl indenones, synthesized through our newly developed copper-catalyzed radical cascade cyclization strategy, were found to own typical aggregation-induced emission (AIE) properties, showing orange to red emission with large Stokes shift (more than 135 nm). In addition, such newly found AIEgens could be successfully used in live cell imaging, exhibiting excellent biocompatibility and application potential.

4.
J Org Chem ; 83(19): 11727-11735, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30160484

RESUMO

An effective radical cascade cyclization strategy was developed, by which a wide range of 2-phosphoryl-substituted quinoxalines were prepared in one pot via reaction of ortho-diisocyanoarenes with diarylphosphine oxides in the presence of AgNO3 under mild reaction conditions.

5.
Gene ; 668: 48-53, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29775756

RESUMO

Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells. Recent years, more and more research suggested PKM2 plays a crucial role in cancer progression through both metabolic and non-metabolic pathways. On the one hand, the middle product of glycolysis, such as amino acids, nucleotides, lipids is necessary to rapid growth of cancer cells. On the other hand, PKM2 supports tumor growth through regulating the expression of gene that involved in cell proliferation, migration and apoptosis. In this article, we review the recent advances to further understand the regulation and function of PKM2 in tumorigenesis. Given its multiple effects on cancer, PKM2 may be a potential target for cancer diagnosis and treatment.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias/enzimologia , Hormônios Tireóideos/metabolismo , Carcinogênese , Regulação da Expressão Gênica , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia
6.
World J Gastroenterol ; 23(6): 986-998, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28246472

RESUMO

AIM: To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin. METHODS: Hepatoma cells, HepG2, were cultured in vitro. Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes' expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis. RESULTS: In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed. CONCLUSION: These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis.


Assuntos
Fator 6 Ativador da Transcrição/antagonistas & inibidores , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ciclo-Oxigenase 2/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Melatonina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Fator 6 Ativador da Transcrição/genética , Regulação para Baixo , Células Hep G2 , Humanos , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Tunicamicina/farmacologia , Proteína X Associada a bcl-2/metabolismo
7.
Med Oncol ; 34(3): 32, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28132115

RESUMO

Esophageal cancer is one of the most common malignant tumors in the world, and its incidence is the eighth highest; meanwhile, its fatality rate is the sixth highest. The PI3K/Akt/mTOR signaling pathway plays a required role in human cancer, including cell survival, metabolism and migration. As a kind of important scaffold protein in mTORC2, RICTOR has showed over-expression in several malignancies like melanoma and endometrial cancer. In this research, we selected 201 cases of paraffin specimens from patients diagnosed as esophageal squamous cell carcinoma after surgical treatment and then estimated the RICTOR expression in each esophageal squamous cell carcinoma tissue by using the immunohistochemical streptavidin-peroxidase technique. Then, we analyzed the association among the clinicopathological parameters, the prognosis and the expression of RICTOR. Eventually, we found that the percentage of RICTOR-positive expression in 201 ESCC samples is 70.6% (142/201) and the figure for RICTOR-negative or RICTOR-doubtful-positive expression is 29.4% (59/201). RICTOR expression positively correlated with ESCC patients' AJCC stage (P = 0.011) and showed an opposite trend with survival (P = 0.007). Based on univariate and multivariate Cox proportional hazards regression analysis, RICTOR-positive expression, AJCC staging III or IV and nodal metastasis are prognostic factors and the former two are independent risk factors for ESCC. In conclusion, our study showed potential that targeting RICTOR may represent new effective inhibitors for treating ESCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/biossíntese , Neoplasias Esofágicas/metabolismo , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteína Companheira de mTOR Insensível à Rapamicina , Taxa de Sobrevida
8.
Oncotarget ; 8(68): 113185-113193, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29348897

RESUMO

The survival time of patients with early clear cell renal cell carcinoma (ccRCC) is fairly long, but 20% to 30% of patients with localized tumors experience relapse, and the effect of IFN-α on survival has not been well studied in patients with early ccRCC. In this study, 208 patients with early ccRCC were treated with surgery, and 54 of the patients received IFN-α as adjuvant therapy. The remaining 115 patients were treated with surgery but not with IFN-α therapy. The primary endpoint was the recurrence rate, 20.37% (11/54) and 33.04% (38/115) in the IFN-α and surgery-only group, respectively. The secondary endpoint was progression-free survival (PFS), which was 123.70 (95% CI: 107.18-140.22) months for the IFN-α group, and 95.80 (95% CI: 82.18-109.42) months for the non-IFN-α group; this difference was significant (P < 0.05). The main side effects were pyrexia (61.11%), muscle pain (24.07%), malaise (9.26%), anorexia (5.56%), hepatic dysfunction (3.70%) and renal dysfunction (1.85%). Moreover, a multivariate regression identified older age, higher BMI index and smoking as significant and independent predictors of decreased PFS (P < 0.05). Overall, IFN-α therapy significantly improved PFS in Chinese patients with early ccRCC and was an independent prognostic factor (P < 0.05). In conclusion, our study showed that adjuvant IFN-α therapy decreased the recurrence rate and prolonged PFS in patients with ccRCC. Thus, this treatment may help clinicians to select a better treatment modality and better predict survival in these patients.

9.
Am J Cancer Res ; 6(2): 226-37, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27186398

RESUMO

Cholangiocarcinoma (CCA), the most common biliary tract malignancy, is arising from the bile duct epithelium with the global significantly increased morbidity and mortality. Here, we showed the effect of guggulsterone, a steroid found in the resin of the guggul plant, on human HuCC-T1 and RBE CCA cells. Exposure to various concentrations of guggulsterone for multiple action time resulted in significant apoptosis in the CCA cells via activating both extrinsic and intrinsic pathways. Furthermore, we demonstrated that the apoptosis of CCA cells was induced by Reactive oxygen species (ROS) mediated JNK signaling pathway. Consistently, inhibition of JNK activity, overexpression of JBD, its binding protein or reduction of ROS by overexpression of catalase, all decreased apoptotic cells. Our results also revealed that guggulsterone-induced apoptosis was coupled with endoplasmic reticulum stress (ERS) in CHOP-dependent pathway. Downregulation of CHOP instead of other ERS markers could inhibit CCA cell apoptosis. Taken together, our results showed that guggulsterone could induce apoptosis of human CCA cells through ROS/JNK signaling pathway, indicating that guggulsterone could be important for the clinical therapy of CCA.

10.
Oncotarget ; 7(17): 24585-95, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27029054

RESUMO

Several clinical trials indicate that concurrent administration of tyrosine kinase inhibitors (TKIs, such as gefitinib or erlotinib) with chemotherapy agents fails to improve overall survival in advanced non-small cell lung cancer (NSCLC) patients. However, the precise mechanisms underlying the antagonistic effects remain unclear. In the present study, we investigated the role of exosomes in the antagonistic effects of concurrent administration of chemotherapy and TKIs. Exosomes derived from gefitinib-treated PC9 cells (Exo-GF) decreased the antitumor effects of cisplatin, while exosomes derived from cisplatin-treated PC9 cells (Exo-DDP) did not significantly affect the antitumor effects of gefitinib. Additionally, inhibition of exosome secretion by GW4869 resulted in a modest synergistic effect when cisplatin and gefitinib were co-administered. Furthermore, Exo-GF co-incubation with cisplatin increased autophagic activity and reduced apoptosis, as demonstrated by an upregulation of LC3-II and Bcl-2 protein levels and downregulation of p62 and Bax protein levels. Thus, the antagonistic effects of gefitinib and cisplatin were mainly attributed to Exo-GF, which resulted in upregulated autophagy and increased cisplatin resistance. These results suggest that inhibition of exosome secretion may be a helpful strategy to overcome the antagonistic effects when TKIs and chemotherapeutic agents are co-administered. Before administering chemotherapy, introducing a washout period to completely eliminate TKI-related exosomes, may be a better procedure for administering chemotherapy and TKIs.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Receptores ErbB/metabolismo , Exossomos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/farmacologia , Autofagia/efeitos dos fármacos , Receptores ErbB/genética , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Regulação para Cima
11.
Oncol Lett ; 10(3): 1416-1422, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26622683

RESUMO

Guggulsterone has recently been reported to demonstrate anti-tumor effects in a variety of cancers. The present study aims to investigate the biological roles and underlying mechanism of the action of guggulsterone in cholangiocarcinoma. The immortalized human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell lines were treated with various concentrations of the trans isomer of guggulsterone, Z-guggulsterone. Cellular proliferation was determined using the XTT assay. The apoptotic status of cholangiocarcinoma cells was assessed by Hoechst 33258 staining, DNA fragmentation assay and flow cytometry. Specific caspase inhibitor was used to explore the role of caspase in guggulsterone-induced apoptosis. A colorimetric assay was performed to measure the alterations of the activities of caspase-3, -8 and -9. Western blot analysis was used to detect the protein expression of survivin, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP). As revealed by the present data, guggulsterone significantly inhibited the growth of the two human cholangiocarcinoma cell lines by inducing cellular apoptosis. In addition, guggulsterone-induced apoptosis of cholangiocarcinoma cells was demonstrated to be partially inhibited by the caspase inhibitors z-VAD-fmk, z-LEHD-fmk and z-IETD-fmk, accompanied by the activation of caspases-3, -8 and -9, accumulation of cleaved PARP and decreased expression of survivin and Bcl-2. In conclusion, the present study demonstrated that guggulsterone was able to suppress the proliferation of cholangiocarcinoma by inducing caspase-dependent apoptosis and downregulating survivin and Bcl-2.

12.
Clin Lung Cancer ; 16(5): e55-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25979647

RESUMO

BACKGROUND: Four large clinical trials have shown that concurrent administration of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), such as gefitinib or erlotinib, with chemotherapy agents does not improve overall survival (OS) in unselected patients with advanced non-small-cell lung cancer (NSCLC). In the present study, the role of autophagy in the combination of gefitinib and cisplatin on EGFR-TKI-sensitive human lung cancer cell line was investigated. Moreover, whether simultaneous autophagy inhibition treatment increases the antitumor activity was explored. MATERIALS AND METHODS: The PC9 cell was exposed to either gefitinib or cisplatin alone or together. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cytotoxic interaction between gefitinib and cisplatin was determined using coefficient of drug interaction (CDI) analysis. The cell cycle distribution and apoptosis were measured using flow cytometry. Alterations in the autophagy and apoptosis signaling pathway were measured using Western blot assays. RESULTS: Coadministration of gefitinib and cisplatin resulted in antagonistic activity to tumor cell proliferation. However, the addition of chloroquine (CQ), an autophagy inhibitor, overcame the antagonistic effects, as demonstrated by CDI analysis and Annexin V-FITC/propidium iodide (PI) assays. In addition, gefitinib administration led to cell G1 phase arrest, which might have contributed to the antagonistic activity between gefitinib and cisplatin. However, the addition of CQ did not deregulate cell cycle arrest, indicating that other mechanisms might be involved. The Annexin V-FITC/PI assays showed that the addition of CQ significantly the increased the ratio of apoptosis cells. Also, immunoblotting assays exhibited increased Bax and decreased Bcl-2, suggesting that autophagy inhibition by CQ could increase cell apoptosis and thus overcome the antagonistic effects. CONCLUSION: The combination of gefitinib with cisplatin generates antagonistic effects on EGFR-TKI-sensitive cells. However, inhibiting autophagy produces a synergistic effect, suggesting that gefitinib and cisplatin combined with an autophagy inhibitor (especially CQ) might be a beneficial strategy to overcome the antagonistic effects between EGFR-TKIs and chemotherapeutic agents.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloroquina/farmacologia , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Receptores ErbB/genética , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/administração & dosagem
13.
Oncol Rep ; 30(1): 433-40, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23673668

RESUMO

Endoplasmic reticulum (ER) stress and autophagy are important adaptive responses in eukaryotes. The aim of this study was to investigate the autophagic responses in hepatocellular carcinoma (HCC) cells under ER stress and the effect of autophagy on cell survival and death. The human HCC cell line HepG2 was stimulated with tunicamycin to induce ER stress. Cell viability was detected using the Cell Counting Kit-8. The accumulation of autophagic compartments was observed using transmission electron microscopy. The expression of ER and autophagy-related proteins was assessed by western blotting. Autophagic flux was assessed by microtubule-associated protein 1-light chain 3 (MAP1-LC3) turnover assay in the presence of chloroquine to inhibit lysosomes. HepG2 cells subjected to the ER stress presented a significant accumulation of autophagosomes and increased conversion of LC3-I to LC3-II as well as enhanced autophagic flux as detected by the LC3 turnover assay. Inhibition of autophagy with 3-methyladenine facilitated ER stress-related cell death. We conclude that ER stress enhances the autophagic flux in HepG2 cells, which may contribute to the maintenance of cell viability.


Assuntos
Autofagia/fisiologia , Carcinoma Hepatocelular/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Neoplasias Hepáticas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Células Hep G2 , Humanos , Fagossomos/metabolismo , Tunicamicina
14.
Mol Biol Rep ; 40(1): 109-16, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23160898

RESUMO

Published data on the association between miR-196a2 rs11614913 polymorphism and risk of gastrointestinal (GI) cancers are inconsistent among studies. To clarify the association, we performed a comprehensive literature search and a meta-analysis. We searched multiple databases to identify genetic association studies investigating the effect of miR-196a2 rs11614913 polymorphism on GI cancers with the last report up to January 18, 2012. The odds ratio (OR) and its 95 % confidence interval (95 % CI) were calculated to assess the strength of association. A total of 13 studies including 4,947 cases and 5,642 controls based on the search criteria were involved in this meta-analysis. In the overall analysis, it was suggested that variant C allele of miR-196a2 rs11614913 polymorphism could significantly increase risk of GI cancers in different genetic models (C vs T: OR = 1.17, 95 % CI = 1.07-1.28, P = 0.0008; CT + CC vs TT: OR = 1.26, 95 % CI = 1.08-1.48, P = 0.004; CC vs CT + TT: OR = 1.23, 95 % CI = 1.08-1.39, P = 0.002; CC vs TT: OR = 1.55, 95 % CI = 1.24-1.94, P = 0.0001; CT vs TT: OR = 1.20, 95 % CI = 1.02-1.40, P = 0.03). When stratified by ethnicity, we found a significant association in Asian population, as well as Caucasian population. When stratified by cancer types, we found a significant association in colorectal cancer, as well as esophageal cancer. We did not find a significant association between miR-196a2 rs11614913 polymorphism and hepatocellular carcinoma risk. For gastric cancer, a significantly increased cancer risk was observed only in homozygote comparison. This meta-analysis demonstrates that miR-196a2 rs11614913 polymorphism is significantly associated with risk of GI cancers.


Assuntos
Neoplasias Gastrointestinais/genética , MicroRNAs , Polimorfismo de Nucleotídeo Único , Grupos de Populações Continentais/genética , Genótipo , Humanos , Viés de Publicação , Risco
15.
World J Gastroenterol ; 16(35): 4483-90, 2010 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-20845518

RESUMO

AIM: To investigate the anti-tumor effects of paeonol in gastric cancer cell proliferation and apoptosis in vitro and in vivo. METHODS: Murine gastric cancer cell line mouse forestomach carcinoma (MFC) or human gastric cancer cell line SGC-7901 was cultured in the presence or absence of paeonol. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell cycle and apoptosis by flow cytometry and TUNEL staining. Tumor growth after subcutaneous implantation of MFC cells in mice was monitored, and the effects of treatment with paeonol were determined. RESULTS: In vitro, paeonol caused dose-dependent inhibition on cell proliferation and induced apoptosis. Cell cycle analysis revealed a decreased proportion of cells in G0/G1 phase, with arrest at S. Paeonol treatment in gastric cancer cell line MFC and SGC-790 cells significantly reduced the expression of Bcl-2 and increased the expression of Bax in a concentration-related manner. Administration of paeonol to MFC tumor-bearing mice significantly lowered the tumor growth and caused tumor regression. CONCLUSION: Paeonol has significantly growth-inhibitory and apoptosis-inducing effects in gastric cancer cells both in vitro and in vivo.


Assuntos
Acetofenonas/uso terapêutico , Neoplasias Gástricas , Acetofenonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Proteína X Associada a bcl-2/metabolismo
16.
World J Gastroenterol ; 16(12): 1473-81, 2010 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-20333787

RESUMO

AIM: To investigate whether melatonin has synergistic effects with doxorubicin in the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and Bel-7402. METHODS: The synergism of melatonin and doxorubicin inhibited the cell growth and induced cell apoptosis in human hepatoma cell lines HepG2 and Bel-7402. Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using TUNEL method and flow cytometry. Apoptosis-related protein Bax, Bcl-2 and caspase-3 expressions were measured by immunohistochemical staining. RESULTS: Treatment with melatonin (10(-8)-10(-5) mol/L) alone had a dose-related inhibitory effect on cell proliferation but no cytotoxic effect on hepatoma cell lines HepG2 and Bel-7402. Interestingly, when combined with doxorubicin, melatonin significantly increased the effects of cell growth inhibition and cell apoptosis. Furthermore, TUNEL staining and flow cytometry revealed that cooperative apoptosis induction was associated with decreased expression of Bcl-2 as well as increased expression of Bax and Caspase3. CONCLUSION: The synergism of melatonin and doxorubicin inhibits hepatoma cell growth and induces cell apoptosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Antibióticos Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Citometria de Fluxo , Células Hep G2 , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas/metabolismo , Melatonina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA