Effect and mechanism of protease inhibitor oprozomib on doxorubicin sensitivity of hepatocellular carcinoma cells

Abstract

This study was to examine the impact of Oprozomib (OPZ), an oral second-generation proteasome inhibitor, on the sensitivity of hepatocellular carcinoma (HCC) cells to doxorubicin (DOX), a commonly used chemotherapy drug for the treatment of HCC. HCC cells were incubated with OPZ or DOX. Cell proliferation was assessed using MTT and colony formation assay, while cell migration and invasion were evaluated using scratch assay and Transwell assay. Cell apoptosis was measured using flow cytometry, and apoptosis-related molecules were determined through Western blot analysis. The proliferation, migration, and invasion of HCC cells were effectively suppressed by OPZ in a dose-dependent manner. This inhibition was achieved through the upregulation of pro-apoptotic genes, resulting in the promotion of apoptosis. Furthermore, OPZ significantly augmented the cytotoxicity and apoptosis induced by DOX. OPZ alone can effectively inhibit cell proliferation and induce apoptosis. OPZ can enhance DOX sensitivity and cellular apoptosis.

Keywords

• doxorubicin
• hepatocellular carcinoma
• drug resistance
• protease inhibitor
• oprozomib
• proapoptotic gene