期刊
ONCOLOGY REPORTS
卷 36, 期 2, 页码 845-852出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2016.4839
关键词
gallbladder cancer; proteasome inhibitor; TRAIL; DR5; apoptosis
类别
资金
- Minhang District Natural Science Foundation of Shanghai [2012MHZ025]
- Public Health Bureau Youth Foundation of Shanghai [20134Y089]
- Natural Science Foundation of Shanghai [12nm0502202, 114119a4700]
- Pudong New Area Science and Technology Development Fund [PKJ2012-Y24]
- Pudong New Area Health System discipline lead development program [PWRd2013-10]
TRAIL is a tumor-selective apoptosis-inducing cytokine playing a vital role in the surveillance and elimination of some tumor cells. However, some tumors are resistant to TRAIL treatment. Proteasome inhibitor MG132 exhibits anti proliferative and pro-apoptotic properties in many tumors. In this study, we demonstrated that proteasome inhibitor MG132 in vitro and in vivo potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells. MG132 was able to inhibit the proliferation of GBC-SD cells and induce apoptosis in a dose-dependent manner. The induction of apoptosis by proteasome inhibitor MG132 was mainly through the extrinsic apoptotic pathways of caspase activation such as caspase-8, caspase-3 and PARP cleavage. In addition, this process was also dependent on the upregulation of death receptor 5 (DR5), which promoted TRAIL-induced apoptosis in GBC-SD cells. Taken together, these findings indicate that MG132 possesses anti-gallbladder cancer potential that correlate with regulation of DR5-dependent pathway, and suggest that MG132 may be a promising agent for sensitizing GBC-SD cells to TRAIL-induced apoptosis.
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