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Proteasome Inhibitors Sensitize Hepatocellular Carcinoma Cells to TRAIL
作者姓名:Qingfeng  Sheng  Yurong  Shi  Qiang  Li  Jihui  Hao  Ruifang  Niu  Xiyin  Wei  Yi  Yang  Lin  Zhang
作者单位:Qingfeng Sheng1 Yurong Shi2 Qiang Li1 Jihui Hao1 Ruifang Niu2 Xiyin Wei2 Yi Yang2 Lin Zhang2 1 Department of Hepatobiliary Oncology,Tianjin Cancer Institute and Hospital. Tianjin 300060,China. 2 Oncology Central Laboratory,Tianjin Cancer Institute and Hospital. Tianjin 300060,China.
基金项目:This work was supported by grants fromTianjin Education Commission, China(No.20040217).
摘    要:A poptosis, an evolutionarily conserved form of cell suicide, oc- curs in two physiological stages: commitment and execution.1] It has been found that several Bcl-2 family proteins are located in the outer mitochondrial membrane, where they control relea…

关 键 词:肝癌  抑制剂  降解方法  诊断方法  肿瘤
收稿时间:2006-08-21
修稿时间:2006-10-20

Proteasome inhibitors sensitize hepatocellular carcinoma cells to TRAIL
Qingfeng Sheng Yurong Shi Qiang Li Jihui Hao Ruifang Niu Xiyin Wei Yi Yang Lin Zhang.Proteasome Inhibitors Sensitize Hepatocellular Carcinoma Cells to TRAIL[J].Chinese Journal of Clinical Oncology,2006,3(6):442-446.
Authors:Qingfeng Sheng  Yurong Shi  Qiang Li  Jihui Hao  Ruifang Niu  Xiyin Wei  Yi Yang  Lin Zhang
Institution:1. Department of Hepatobiliary Oncology,Tianjin Cancer Institute & Hospital, Tianjin 300060, China
2. Oncology Central Laboratory, Tianjin Cancer Institute & Hospital, Tianjin 300060, China
Abstract:OBJECTIVE To investigate the effect of proteasome inhibition on the sensitivity of carcinoma cells to TRAIL-inducing apoptosis, and to study the mechanism of the response. METHODS Human hepatocellular carcinoma cells, pretreated with the proteasome inhibitor, MG132, were cotreated with TRAIL. Western blot assays, immunoprecipitation and RT-PCR were performed to test the expression of the Bcl-2 family proteins and Bax mRNA. RESULTS We found that (i) proteasome inhibition sensitized the human hepatocellular carcinoma cells to TRAIL; and (ii) resulted in Bax accumulation before release of cytochrome C and induction of apoptosis. These results were associated with the ability of proteasome inhibitors to overcome Bcl-2-mediated antiapoptotic function; (iii) Bax is regulated by an ubiquitin/proteasome-dependent degradation pathway. CONCLUSION Proteasome inhibition sensitized hepatocellular carcinoma cells to TRAIL by the inhibition of the ubiquitin/proteasome-mediated Bax degradation pathway.
Keywords:proteasome inhibitor  TRAIL  apoptosis  hepatocellulr carcinoma  
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