Zoledronic acid influences growth, migration and invasive activity of prostate cancer cells in vitro.

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 ß 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 ß1-integrin in PC-3 and diminished ß4-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.