RT Journal Article
SR Electronic
T1 Proteasome Inhibitors Sensitize Hepatocellular Carcinoma Cells to TRAIL
JF Chinese Journal of Clinical Oncology
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 442
OP 446
VO 3
IS 6
A1 Sheng, Qingfeng
A1 Shi, Yurong
A1 Li, Qiang
A1 Hao, Jihui
A1 Niu, Ruifang
A1 Wei, Xiyin
A1 Yang, Yi
A1 Zhang, Lin
YR 2006
UL http://www.cancerbiomed.org/content/3/6/442.abstract
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.