Most advanced prostate cancers progress to castration resistant prostate cancer (CRPC) after a few years of androgen deprivation\r\ntherapy and the prognosis of patients with CRPC is poor. Although docetaxel and cabazitaxel can prolong the survival of patients\r\nwith CRPC, inevitable progression appears following those treatments. It is urgently required to identify better or alternative\r\ntherapeutic strategies. The purpose of this study was to confirm the anti-cancer activity of zoledronic acid (Zol) and determine\r\nwhether inhibition of geranylgeranylation in the mevalonate pathway could be a molecular target of prostate cancer treatment.\r\nWe examined the growth inhibitory effect of Zol in prostate cancer cells (LNCaP, PC3, DU145) and investigated a role of\r\ngeranylgeranylation in the anticancer activity of Zol.We, then, evaluated the growth inhibitory effect of geranylgeranyltransferase\r\ninhibitor (GGTI), and analyzed the synergy of GGTI and docetaxel by combination index and isobolographic analysis. Zol\r\ninhibited the growth of all prostate cancer cell lines tested in a dose-dependent manner through inhibition of geranylgeranylation.\r\nGGTI also inhibited the prostate cancer cell growth and the growth inhibitory effect was augmented by a combination with\r\ndocetaxel. Synergism between GGTI and docetaxel was observed across a broad range of concentrations. In conclusion, our results\r\ndemonstrated that GGTI can inhibit the growth of prostate cancer cells and has synergistic effect with docetaxel, suggesting its\r\npotential role in prostate cancer treatment.
Loading....