Antitumor effect of the angiogenesis inhibitor agm-1470 and its combination effect with tamoxifen in dmba induced mammary-tumors in rats.

AGM-1470 is known to inhibit angiogenesis. It inhibited the mitogen induced cell growth in microvascular endothelial cells in vitro. Ten ng/ml AGM-1470 completely inhibited both basic fibroblast growth factor induced cell growth, and interleukin-4 induced cell growth. In an in vivo study, we invesigated the antitumor effect of AGM-1470 in dimethylbenz[a]anthracene (DMBA) induced rat mammary tumors. A dose dependent growth inhibition was seen between administered doses 10 mg/kg and 40 mg/kg. Forty mg/kg 2-week administration of AGM-1470 totally suppressed the tumor growth. In addition, an additive inhibitory effect of AGM-1470 with an antiestrogen tamoxifen was found (p<0.01). It is suggested that the combination of these two drugs might be effective for the treatment of breast cancer.