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.

Written by:
Mani J, Vallo S, Barth K, Makarević J, Juengel E, Bartsch G, Wiesner C, Haferkamp A, Blaheta RA. Are you the author?
Department of Urology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.

Reference: Prostate Cancer Prostatic Dis. 2012 Mar 27. Epub ahead of print.
doi: 10.1038/pcan.2012.9

PubMed Abstract
PMID: 22450844

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