Effect of zoledronic acid combined with cisplatin for non-small cell lung cancer

Abstract

19116 Background: Matsumoto et al (Matsumoto, Kimura et al. 2005) investigated the anti-proliferative effects of zoledronic acid (ZA) as a single agent and in combination with other agents against small cell lung cancer cell lines. Walter Berger,et al (Berger, Kubista et al. 2005) investigated whether ZA exerts anticancer activity against human non-small cell lung cancer (NSCLC) cells. ZA treatment resulted in a potent antiproliferative effect against all investigated NSCLC cell lines independent of their Ras and p53 mutation status.Our object is to study the effect and possible mechanism of Zoledronic acid (ZA) combined with cisplatin (DDP) on human non-small cell lung cancer. Methods: The proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effects of ZA and DDP to neoplasia were verified on subcutaneous implanted tumor of nude mice. Results: Both ZA and DDP could inhibit A549 cell proliferation in a concentration-dependent pattern. When ZA (20μmol/ L) and DDP (>5μmol/ L) were combined, the inhibitory effect was enhanced in a synergistic or additive pattern. Both ZA (20μmol/ L)and DDP(10μmol/ L) could significantly increase the apoptosis of A549 cells ( P<0.05), and this action was remarkably increased when DDP was combined with ZA (P<0.05). ZA and DDP could inhibit the growth of subcutaneous implanted tumor on nude mice and the inhibitory rate of ZA combined with DDP was significantly higher than that of ZA or DDP alone (P<0.05). Conclusions: Zoledronic acid combined with DDP shows significantly synergistic anti-tumor effects on lung cancer cell line A549 and subcutaneous implanted tumor on nude mice, which may be achieved by enhancement of growth inhibition and apoptosis induction to tumor cells. No significant financial relationships to disclose.