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Exp Eye Res ; 113: 128-34, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23727160

RESUMO

Simvastatin is a cholesterol-lowering drug which exhibits numerous pleiotropic effects including anti-cancer activity. Yet, the anti-cancer effects in choroidal melanoma remain poorly characterized. Therefore, in this study, we investigated the effects of simvastatin on OCM-1 cells growth, apoptosis and cycle. Simvastatin showed an inhibitory effects on OCM-1 cells viability in dose-dependent (2-10 µM) and time-dependent (24-72 h) manner. Further study suggested that simvastatin-induced inhibition OCM-1 cells proliferation was associated with G1 phase arrest, decreased protein and mRNA expression of proliferation marker cyclin D1, cyclin E, cyclin dependent kinase (CDK)2 and increased expression of CDK inhibitory protein P21. In addition, simvastatin resulted in an increase in levels of reactive oxygen species (ROS) in OCM-1 cells and simvastatin significantly triggered apoptosis in OCM-1 cells, which was characterized by increased chromatin condensation, activation of caspase-9 and cleaved-caspase-3, increased expression mitochondrion-related apoptosis protein of P53, Bax and decreased expression of Bcl2 and iASPP. Collectively, our study demonstrated that simvastatin can efficiently inhibit proliferation and induce apoptosis in OCM-1 cells.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Neoplasias da Coroide/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Melanoma/patologia , Sinvastatina/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Western Blotting , Caspase 3/metabolismo , Caspase 9/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias da Coroide/enzimologia , Ciclina E/metabolismo , Ciclina E/farmacologia , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fase G1/efeitos dos fármacos , Humanos , Melanoma/enzimologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Oncogênicas , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , Proteína X Associada a bcl-2/metabolismo
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