Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model.
Clinically obtainable concentrations of zoledronic acid (ZOL) inhibited the production of vascular endothelial growth factor and reduced the migration, adhesion, and invasiveness of osteosarcoma (OS) cells in vitro. The in vivo effects of ZOL were investigated by using a murine model of spontaneous lung metastasis. The higher dose of ZOL (80 microg/kg three times/week) inhibited the growth of OS at the primary site, accompanied by inhibition of neovascularization in the tumor. Interestingly, while the lower dose of ZOL (80 microg/kg once a week) could not inhibit the growth of OS at the primary site, it significantly prevented lung metastasis.
Koto
Kazutaka
K
Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Horie
Naoyuki
N
Kimura
Shinya
S
Murata
Hiroaki
H
Sakabe
Tomoya
T
Matsui
Takaaki
T
Watanabe
Motonobu
M
Adachi
Souichi
S
Maekawa
Taira
T
Fushiki
Shinji
S
Kubo
Toshikazu
T
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D017368:Protein Prenylation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D042461:Vascular Endothelial Growth Factor A; D000077211:Zoledronic Acid