Effects of angiogenesis inhibitor TNP-470 on tamoxifen-stimulated MCF-7 breast tumors in nude mice

The antitumor effect of TNP-470, antiangiogenic drug, was analyzed in the tamoxifen-stimulated MT-2 tumors inoculated in the athymic nude mice. TNP-470 was injected subcutaneously at a dose of 30 mg/kg body weight twice a week to mice which were randomized into three treatments: control (sham treatment), tamoxifen alone, and tamoxifen plus TNP-470. TNP-470 inhibited the growth of the tamoxifen-stimulated MT2 tumors without any major side effects or significant weight loss compared with tamoxifen-treated mice alone. The mean tumor area of the mice treated with tamoxifen plus TNP-470 was reduced 50% to those treated with tamoxifen alone. TNP-470 was shown to inhibit tumor neovascularization and to increase incidence of apoptosis in tumor cells. TNP-470 did not affect tamoxifen metabolism of the mice. In conclusion, TNP-470 could be evaluated clinically in patients with tamoxifen failure.