PT  - JOURNAL ARTICLE
AU  - Sheng, Qingfeng
AU  - Shi, Yurong
AU  - Li, Qiang
AU  - Hao, Jihui
AU  - Niu, Ruifang
AU  - Wei, Xiyin
AU  - Yang, Yi
AU  - Zhang, Lin
TI  - Proteasome Inhibitors Sensitize Hepatocellular Carcinoma Cells to TRAIL
DP  - 2006 Dec 01
TA  - Chinese Journal of Clinical Oncology
PG  - 442--446
VI  - 3
IP  - 6
4099  - http://www.cancerbiomed.org/content/3/6/442.short
4100  - http://www.cancerbiomed.org/content/3/6/442.full
SO  - Cancer Biol Med2006 Dec 01; 3
AB  - 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.