Proteasome inhibitor MG132 potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells via DR5-dependent pathway

Zhu,Weiping; Zhan,Dihua; Wang,Lu; Ma,Dening; Cheng,Mingrong; Wang,Huipeng; Zhao,Jiaying; Cai,Yuankun; Cheng,Zhijian

doi:10.3892/or.2016.4839

Proteasome inhibitor MG132 potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells via DR5-dependent pathway

Authors:
- Weiping Zhu
- Dihua Zhan
- Lu Wang
- Dening Ma
- Mingrong Cheng
- Huipeng Wang
- Jiaying Zhao
- Yuankun Cai
- Zhijian Cheng
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Affiliations: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China, Department of Liver Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China, Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai 201318, P.R. China, Department of General Surgery, The Affiliated Shanghai Fifth People's Hospital of Fudan University, Shanghai 200240, P.R. China
Published online on: May 27, 2016 https://doi.org/10.3892/or.2016.4839
Pages: 845-852

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Abstract

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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