Effects of tamoxifen and interferon-β or the combination on tumor-induced angiogenesis

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Abstract
Inhibition of angiogenesis by anti-tumor agents may play a role in tumor growth arrest. Tamoxifen and interferon-α/β (IFN-α/β) exhibit potentiated anti-proliferative activity against tumor cells. However, additional host-mediated effects such as modulation of angiogenesis may also inhibit tumor growth in vivo. The effect of tamoxifen and IFN-β on angiogenesis induced by 2 human tumors, MCF-7 breast carcinoma (estradiol dependent) and NIH-OVCAR-3 ovarian carcinoma (estradiol independent), was assessed. Treatment of nude mice bearing MCF-7 tumors with tamoxifen resulted in a 68% decrease in the number of vessels at the tumor periphery. Treatment with IFN-β yielded a 33% reduction. Treatment of nude mice bearing NIH-OVCAR-3 tumors with tamoxifen resulted in a 73% decrease in the number of vessels. Treatment with IFN-β yielded a 57% reduction. Combination treatment resulted in augmented anti-angiogenic effects. As single agents, both tamoxifen and IFN-β inhibited xenograft tumor growth. Ten weeks of tamoxifen treatment resulted in growth inhibition of MCF-7 and NIH-OVCAR-3 carcinomas by 85% and 66%, respectively. Ten weeks of IFN-β treatment resulted in inhibition of growth of MCF-7 and NIH-OVCAR-3 carcinomas by 67% and 88%, respectively. The combination of tamoxifen and IFN-β completely prevented growth of MCF-7 and NIH-OVCAR-3 carcinomas. The anti-angiogenic effects of tamoxifen and IFN-β were additive. Inhibition of angiogenesis was detectable before measurable effects on tumor volume in both MCF-7 and NIH-OVCAR-3 tumors. Potentiation of anti-angiogenic effects by tamoxifen and IFN-β, possibly resulting from enhanced IFN-induced gene expression, may contribute to anti-tumor activity in both estradiol-dependent and estradiol-independent tumors in vivo. Int. J. Cancer 71:456-461, 1997. © 1997 Wiley-Liss Inc.