title: Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medical Oncology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Salvatore
authors.forename: A
authors.initials: A
authors.lastname: Orlandi
authors.forename: C
authors.initials: C
authors.lastname: Bagalà
authors.forename: M
authors.initials: M
authors.lastname: Quirino
authors.forename: A
authors.initials: A
authors.lastname: Cassano
authors.forename: A
authors.initials: A
authors.lastname: Astone
authors.forename: C
authors.initials: C
authors.lastname: Barone
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use*; D016193:G1 Phase; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D020533:Angiogenesis Inhibitors; C107489:BIRC5 protein, human; D016213:Cyclins; D004164:Diphosphonates; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D000077211:Zoledronic Acid