Genistein and AG1024 synergistically increase the radiosensitivity of prostate cancer cells.

Abstract

Radiosensitivity of prostate cancer (PCa) cells promotes the curative treatment for PCa. The present study was designed to investigate the synergistic effect of genistein and AG1024 on the radiosensitivity of PCa cells. The optimal X-irradiation dose (4 Gy) and genistein concentration (30 µM) were selected by using the CCK-8 assay. Before X-irradiation (4 Gy), PC3 and DU145 cells were treated with genistein (30 µM), AG1024 (10 µM) and their combination. All treatments significantly reduced cell proliferation and enhanced cell apoptosis. Using flow cytometric analysis, we found that genistein arrested the cell cycle at S phase and AG1024 arrested the cell cycle at G2/M phase. Genistein treatment suppressed the homologous recombination (HRR) and the non-homologous end joining (NHEJ) pathways by inhibiting the expression of Rad51 and Ku70, and AG1024 treatment only inhibited the NHEJ pathway via the inactivation of Ku70 as detected by western blot analysis. Moreover, the combination treatment with genistein and AG1024 more effectively radiosensitized PCa cells than single treatments by suppressing cell proliferation, enhancing cell apoptosis and inactivating the HRR and NHEJ pathways. In vivo experiments demonstrated that animals receiving the combination treatment with genistein and AG1024 displayed obviously decreased tumor volume compared with animals treated with single treatment with either genistein or AG1024. We conclude that the combination of genistein (30 µM) and AG1024 (10 µM) exhibited a synergistic effect on the radiosensitivity of PCa cells by suppressing the HRR and NHEJ pathways.