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

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.