ABSTRACT
PURPOSE: The clinical use of the zoledronic acid has been increasing recently, and especially for the treatment of bone metastases. The synergistic effects of zoledronic acid with other chemotherapeutic agents have been shown. However it is not known whether a similar synergistic apoptotic effects exist for a combination therapy of zoledronic acid with radiation. METHODS: The MCF-7 human breast cancer cell lines were treated with 10 micrometer, 50 micrometer or 100 micrometer of zoledronic acid, irradiated with 5 Gy, and they were also treated with a combination of both treatments. The results of the synergistic effect on apoptosis were identified by performing XTT assay, DNA fragmentation assay, FACS analysis and western blot analysis at 24, 48, 72 hours after treatment. RESULTS: Zoledronic acid afftects anti-proliferative and apoptotic effects on MCF-7 breast cancer cell line in a dose-dependent manner. The synergistic cytotoxic effect of zoledronic acid and radiation was noted. The western blot analysis suggested that this synergistic effect has a relationship with the intracellular signal pathway especially with Ras, eventhough Bcl-2 and BAX expressions showed no difference in a zoledronic acid and combination treatment group compared to a control group significantly, CONCLUSION: The combined use of zoledronic acid and radiotherapy shows enhanced in vitro cytotoxicity for the MCF-7 human breast cancer cell line. And in vivo study is under way to elucidate the effect of this combination therapy.