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Clinical Cancer Research Vol. 9, 295-306, January 2003
© 2003 American Association for Cancer Research

Experimental Therapeutics, Preclinical Pharmacology

Zoledronic Acid Exhibits Inhibitory Effects on Osteoblastic and Osteolytic Metastases of Prostate Cancer1

Eva Corey2, Lisha G. Brown, Janna E. Quinn, Martin Poot, Martine P. Roudier, Celestia S. Higano and Robert L. Vessella

Departments of Urology [E. C., L. G. B., J. E. Q., M. P. R., C. S. H., R. L. V.] and Pathology [M. P.], University of Washington, Seattle, Washington 98195

Purpose: In this study we have examined the effects of zoledronic acid (ZA), a new-generation bisphosphonate, on prostate cancer (CaP) cells in vitro, and on both osteoblastic and osteolytic CaP metastases in animal models.

Experimental Design: In vitro, CaP cells were treated with ZA, and the effects on proliferation, cell cycle, and apoptosis were determined. In vivo, PC-3, and LuCaP 23.1 s.c. and tibial tumors were treated with ZA. Effects on bone and tumor were determined by histomorphometry and immunohistochemistry.

Results: ZA decreased proliferation of CaP cells, and caused G1 arrest and apoptosis of CaP cells in vitro. In vivo, s.c. CaP tumor growth was not affected by ZA. However, growth of osteoblastic and osteolytic metastases of CaP was inhibited significantly in vivo. Matrix metalloproteinase-2, matrix metalloproteinase-9, and Cathepsin K levels were decreased in osteolytic bone metastases after ZA administration.

Conclusions: In conclusion, we have shown that ZA has significant antitumor effects on CaP cells in vitro and in vivo. Antiosteolytic activity and the antitumor effects of this compound could benefit CaP patients with bone metastases.




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Copyright © 2003 by the American Association for Cancer Research.