Carboxymethyl benzylamide dextran and tamoxifen combination inhibits tumor growth and angiogenesis.
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 G(0)/G(1) 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.
Bagheri-Yarmand
R
R
Laboratoire d'Oncologie et Imagerie des Tumeurs Solides, Faculté de Médecine de Bobigny, Université Paris 13, France.
Hamma-Kourbali
Y
Y
Bissieres
P
P
Morère
J F
JF
Crépin
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002455:Cell Division; D003169:Complement Inactivator Proteins / Q000627:therapeutic use*; D003911:Dextrans / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology
D016588:Anticarcinogenic Agents; D003169:Complement Inactivator Proteins; D003911:Dextrans; D013629:Tamoxifen; C099253:CMDBS 25