Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer.
OBJECTIVE
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.


METHODS
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 G(1) 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.
Corey
Eva
E
Department of Urology, University of Washington, Seattle, Washington 98195, USA. ecorey@u.washington.edu
Brown
Lisha G
LG
Quinn
Janna E
JE
Poot
Martin
M
Roudier
Martine P
MP
Higano
Celestia S
CS
Vessella
Robert L
RL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism; D002455:Cell Division; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010006:Osteoblasts / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9