Combined Ribociclib and NU7026 administration enhances radio-sensitivity by inhibiting DNA repair in prostate cancer

Abstract

Radiosensitivity is critical for clinical outcomes and overall survival of prostate cancer patients treated with irradiation. Ribociclib and NU7026 have been reported as radiosensitizers in cancer cells, but which are inadequately understood in prostate cancer cells. The present study was performed to investigate the effects of ribociclib, NU7026, and their combination on the radiosensitivity of prostate cancer cells. Optimal combined concentrations of ribociclib and NU7026 with X-irradiation were selected. Flow cytometry, CCK-8 assays, soft agar colony formation, and γH2AX foci formation assays were performed to assess the cell cycle distribution, cell viability, cell proliferation, and DNA damage, respectively. Finally, the expression of proteins related to the cell cycle, DNA repair, and cell death was evaluated by western blot analysis. Ribociclib arrested prostate cell cycle in the G0/G1 phase. Compared with the control, X-irradiation combined with ribociclib or NU7026 significantly decreased cell proliferation, reduced colony formation, and enhanced γH2AX foci formation in PC3 and DU145 cells. Moreover, the protein expression levels of CDK4, p-Rb, cyclin D1, rad51, and DNA-PKcs were significantly decreased, whereas that of Bax was significantly increased.The combination of ribociclib and NU7026 may be a potential strategy for prostate cancer therapy by promoting radiosensitivity.

Keywords: Cell cycle; DNA repair; NU7026; Prostate cancer; Radio-sensitivity; Ribociclib.