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.
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Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, 8258 Olson Pavilion, 303 East Chicago Avenue, IL 60611, Chicago, USA.
Lee
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Cisneros
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Jordan
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D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003510:Cyclohexanes; D005260:Female; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D013629:Tamoxifen / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D003510:Cyclohexanes; D012717:Sesquiterpenes; D013629:Tamoxifen; D000077609:O-(Chloroacetylcarbamoyl)fumagillol