title: Zoledronic acid influences growth, migration and invasive activity of prostate cancer cells in vitro.
abstract: BACKGROUND
  The influence of the bisphosphonate zoledronic acid (ZA) on prostate cancer (PC) growth, adhesion and invasive behavior was investigated.
  
  
  METHODS
  PC-3, DU-145 and LNCaP cells were treated with ZA, and tumor-cell growth was then investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, tumor-cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins, as well as migratory properties of the cells, was evaluated. Integrin β subtypes, integrin-dependent signaling, as well as cell-cycle regulating proteins, were analyzed by western blots.
  
  
  RESULTS
  ZA dose-dependently reduced tumor-cell growth but did not impair tumor-endothelium and tumor-matrix interaction. However, ZA significantly inhibited tumor migration and invasive activity. Cyclin E was reduced by ZA in LNCaP and DU-145, and p21 was elevated in LNCaP cells. p27 was upregulated in all tumor cell lines, compared with the controls. ZA elevated β1-integrin in PC-3 and diminished β4-integrin in PC-3 and DU-145 cells.
  
  
  CONCLUSIONS
  ZA inhibits PC growth and motility but does not influence the mechanical contact between tumor cells and the vascular wall.
authors.affiliation: Department of Urology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Mani
authors.forename: S
authors.initials: S
authors.lastname: Vallo
authors.forename: K
authors.initials: K
authors.lastname: Barth
authors.forename: J
authors.initials: J
authors.lastname: Makarević
authors.forename: E
authors.initials: E
authors.lastname: Juengel
authors.forename: G
authors.initials: G
authors.lastname: Bartsch
authors.forename: C
authors.initials: C
authors.lastname: Wiesner
authors.forename: A
authors.initials: A
authors.lastname: Haferkamp
authors.forename: R A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid