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Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model
Kazutaka Koto ,
Naoyuki Horie ,
Shinya Kimura ,
Hiroaki Murata ,
Tomoya Sakabe ,
Takaaki Matsui ,
Motonobu Watanabe ,
Souichi Adachi ,
Taira Maekawa ,
Shinji Fushiki ,
Toshikazu Kubo
February 2009
February 2009
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Abstract
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.