Modification of angiogenesis factors in cancer patients under bisphosphonate

ABSTRACT

Recently, new experimental data suggested that, besides inhibiting osteoclasts, bisphosphonate may also have an antitumor effect. Antiangiogenic activity is one of the possible mechanisms of anticancer activity attributed to zoledronic acid; an amino-bisphosphonate. The aim of this study was to evaluate the modifications in angiogenic cytokines levels after zoledronic acid infusion. Sixteen cancer patients with bone metastases were intravenously infused with zoledronic acid. They were evaluated prospectively for circulating levels of calcium, vascular endothelial growth factor [VEGF], transforming growth factor beta1 [TGF-beta1] and interferon-gamma [IFN-gamma] at different time points just before and after 1 and 7 days of zoledronic acid infusion. Basal VEGF serum levels were decreased significantly on the 1[st] and 7[th] day after zoledronic acid infusion, more pronounced on the 7[th] day. TGF-beta1 serum levels were significantly decreased on the 7[th] day of infusion, while IFN-gamma serum levels were significantly increased 1 day after the infusion. Moreover, the present data showed a statistically significant negative correlation between serum levels of VEGF and of both TGF-beta1 on the 7[th] day of infusion and IFN-gamma on the 1[st] day. This study confirms that the amino-bisphosphonate; zoledronic acid appears to modulate serum levels of proangiogenic growth factors such as VEGF, TGF-beta1 and IFN-gamma in cancer patients. It may have antiangiogenic properties through a significant and lasting decrease in serum levels of VEGF and TGF-beta1. In addition, it may activate the gamma delta T cell population as evidenced by increased INF-gamma level, which shows potential cytotoxic activity toward a broad spectrum of tumors