Abstract
The effect of the potent angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol(TNP-470), a semisynthetic analogue of fumagillin on tumor growth and metastasis was studied using murine mammary tumor cells (JYG-B) inoculated into female nude mice. Injection of TNP-470 at 10 and 30 mg/kg doses, 3 times a week, until the end of the experiment (41 days)inhibited the s.c.inoculated primary tumor growth in a dose-dependent manner (45%and 65% in volume, respectively). TNP-470 at 30 and 60 mg/kg doses, 3 times a week, until the end of the experiment (35 days), reduced the weight of the i.p. inoculated total tumor mass of abdominal dissemination in a dose-dependent manner (54% and 76%, respectively). Pulmonary metastasis was found in all mice but TNP-470 significantly reduced the lung weight reflecting the total volume of the metastatic foci, and the numbers of metastatic foci in the liver and kidneys was reduced by TNP-470 treatment. These findings show that the angiogenesis inhibitor (TNP-470)has a strong inhibitory effect on tumor grwoth and metastasis in vivo.
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