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Carboxymethyl Benzylamide Dextran and Tamoxifen Combination Inhibits Tumor Growth and Angiogenesis¹

Laboratoire d’Oncologie et Imagerie des Tumeurs Solides, Faculté de Médecine de Bobigny, Université Paris 13 [Y. H-K., M. C.]; Laboratoire d’hématologie [P. B.]; and Clinique Universitaire de cancérologie [J-F. M.], 93017 Bobigny Cedex, France; and Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center-108, Houston, Texas 77030 [R. B-Y.]

We showed previously that a carboxymethyl dextran benzylamide (CMDB7) blocks angiogenesis of MDA-MB-435 carcinoma and its lung metastases in nude mice. In this study, we examined the combination effects of CMDB7 and tamoxifen (TAM) on cell proliferation, tumor growth, and angiogenesis on the MCF-7RAS cells. We showed that CMDB7 and TAM acted in a synergistic manner to inhibit the growth of MCF-7RAS cells, blocking them in G₀/G₁ phase of the cell cycle. For 7 weeks, the CMDB7- (300 mg/kg/week) and TAM- (20 mg/kg/week) treated groups showed tumor growth inhibition of about 66% and 76%, respectively. Combined treatments with CMDB7 and TAM block the tumor development by 94% and induce a complete regression of 4 of 8 mice. Histological analysis showed markedly less neovascularization (88%) in the tumors treated with a combination of CMDB7 and TAM. This antiangiogenic activity was further demonstrated by direct inhibition of endothelial cell proliferation. Overall, this study points to the potential use of a combination of CMDB7 and TAM to inhibit tumor angiogenesis that can prevent tumor progression.