Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line

Objectives: Although emerging data suggest that zoledronic acid (Zol) may have different anti‐tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti‐tumoural and anti‐angiogenetic effect of zoledronic acid in non‐small‐cell lung cancer (NSCLC) cells. Material and methods: We treated A549 NSCLC cells with zoledronic acid to investigate survival, cell cycle activity, anti‐angiogenic activity and apoptotic responses to it. Results: We observed that highest Zol concentration (100 μm ) caused arrest in G1 phase of the cell cycle and also induced different percentages of apoptosis in presence (0.9% versus 4.4%) or absence (2.4% versus 28.5%) of serum (P = 0.0001). Zol concentration from 5 to 100 μm for 2 days induced significant concentration‐dependent cell death in adherent cells. Furthermore, Zol (10–100 μm ) induced dose‐dependent reduction both of mRNA and protein expression of VEGF associated with parallel decrease in VEGF secretion in the culture medium. Conclusion: Taken together, these results support a possible anti‐cancer and anti‐angiogenetic activity of Zol. Our data may not only provide a basis for the clinical use of this drug as preventive agent of bone metastases but also suggest that Zol deserves attention as an anti‐cancer agent in non‐small‐cell lung cancer.