Carfilzomib inhibits cell cycle progression at G2/M phase and induces apoptosis in breast cancer cells

Background: Carfilzomib is a second-generation proteasome inhibitor. Lately, it is approved for clinical treatment of multiple myeloma. However, its anti-tumor activity and mechanism against solid tumors has not been elucidated. The study is aimed to investigate the function and the mechanism of Carfilzomib against breast cancer cells. Methods: Breast cancer cell line ZR-75-30 was treated by different concentrations of Carfilzomib. MTT assay was used to examine cell viability. Colony formation assay was performed to detect cell proliferation. Flow cytometry was used to analyze cell cycle and apoptosis, and Hoechst 33258 staining was additionally used to observe cell apoptosis. Western blot was used to detect cell cycle- and apoptosis-associated protein expression level. Results: Carfilzomib impaired viability and colony formation ability of ZR-75-30 breast cancer cell line in a dose-dependent manner. Carfilzomib treatment suppressed protein expression of G2/M checkpoint-specific cyclin-dependent kinase CDK1 (P<0.05) and CDK2 (P>0.05). The pro-apoptotic protein Bax was increased, while the anti-apoptotic proteins Bcl-2 and Mcl-1 were decreased in Carfilzomib-treated cells in a dose-dependent manner. Conclusion: Carfilzomib could inhibit breast cancer cells proliferation and induce cell apoptosis, indicating its potential use for clinical management of breast cancer.