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

• Published in: Oncology reports Vol. 36; no. 2; pp. 845 - 852
• Main Authors: Zhu, Weiping, Zhan, Dihua, Wang, Lu, Ma, Dening, Cheng, Mingrong, Wang, Huipeng, Zhao, Jiaying, Cai, Yuankun, Cheng, Zhijian
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.08.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Cancer therapies; Carcinoma - drug therapy; Carcinoma - metabolism; Caspase 3 - metabolism; Caspase 8 - metabolism; Cell culture; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cytokines; Development and progression; DR5; Drug therapy; Enzyme inhibitors; Gallbladder; Gallbladder - drug effects; Gallbladder cancer; Gallbladder Neoplasms - drug therapy; Gallbladder Neoplasms - metabolism; Genetic aspects; Health aspects; Humans; Leupeptins - pharmacology; Ligands; Medical prognosis; Patient outcomes; Properties; proteasome inhibitor; Proteasome Inhibitors - pharmacology; Proteins; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Signal transduction; TNF-Related Apoptosis-Inducing Ligand - metabolism; TRAIL; Tumor necrosis factor-TNF; Up-Regulation - drug effects; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2016.4839

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.