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

Cell Prolif. 2011 Apr;44(2):139-46. doi: 10.1111/j.1365-2184.2011.00745.x.

Abstract

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 (100μm) 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 100μm for 2 days induced significant concentration-dependent cell death in adherent cells. Furthermore, Zol (10-100μm) 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.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Cyclins / genetics
  • Cyclins / metabolism
  • Diphosphonates / therapeutic use*
  • G1 Phase
  • Humans
  • Imidazoles / therapeutic use*
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lung Neoplasms / drug therapy*
  • Survivin
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Zoledronic Acid

Substances

  • Angiogenesis Inhibitors
  • BIRC5 protein, human
  • Cyclins
  • Diphosphonates
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • Survivin
  • Vascular Endothelial Growth Factor A
  • Zoledronic Acid