Oprozomib inhibits proliferation and promotes apoptosis in gallbladder carcinoma cells through MAPK signaling pathway.

Gallbladder carcinoma (GBC) is the most common malignancy of biliary tract with a dismal prognosis. Previous studies have confirmed that oprozomib has inhibitory effects on a variety of tumors. We aim to investigate the anti-tumor effects of oprozomib on GBC and explore the potential mechanisms. In this study, we demonstrated that oprozomib had significant anti-tumor effect on SGC-996, NOZ, and GBC-SD GBC cell lines in vitro and inhibited GBC tumor growth of SGC-996 and GBC-SD cells xenograft model and exhibited no significant toxicity in vivo. Mechanistically, oprozomib induced SGC-996 and GBC-SD cells G2/M phase arrest through ERK/MAPK signaling pathway as evidenced by the decrease in the expression of CDK1 and Cdc25C, while an increase in the expression of p-ERK, p21, and p27, and apoptosis via JNK/ p38 MAPK signaling pathway as evidenced by an increase in the expression of p-JNK, c-Jun, p-c-Jun, p-p38, Cytochrome c, Cleaved Caspase-8, and Cleaved Caspase-9, while a decrease in the expression of Bcl-2. Oprozomib could induce G2/M phase arrest and apoptosis via MAPK signaling pathway. In addition, our findings provide preclinical evidence for understanding the mechanism and the development of oprozomib-based regimen as a novel potential chemotherapeutic agent against GBC in the future.