The new-generation proteasome inhibitor oprozomib increases the sensitivity of cervical cancer cells to cisplatin-induced apoptosis

Abstract

This study aimed to evaluate the anti-tumor effect of a new generation of protease inhibitor, oprozomib (OPZ), used alone and in combination with cisplatin, also called CDDP, on cervical cancer. Five different types of cervical cancer cell lines - HeLa, Caski, HeLa-CDDP, C33a, and SiHa - and one nontransformed cervical cell line - HaCaT -were treated with OPZ alone or in combination with cisplatin. The inhibitory effects of OPZ and cisplatin on the proliferation of cervical cancer cells were then analyzed using cytotoxicity tests, flow cytometry, and Western blotting. It was found that OPZ alone or in combination with cisplatin can reduce the proliferation of the five types of cancer cells by enhancing the lysis of caspase-3 and PARP and inducing cancer cell apoptosis. In the combined treatment, OPZ was found to inhibit the degradation of inhibitory factor κB alpha induced by cisplatin, thereby inhibiting the activation of NF-κB, which causes cisplatin resistance, and enhancing the sensitivity of the tumor cells to cisplatin. Moreover, OPZ promoted the phosphorylation of the apoptosis signaling pathway JNK that was activated by cisplatin, thereby inducing tumor cell apoptosis. These findings provide a theoretical basis for the clinical use of OPZ alone and in combination with cisplatin in the treatment of cervical cancer.