The antiangiogenic property of docetaxel is synergistic with a recombinanthumanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors

Numerous chemotherapeutic agents have been shown to have an inhibitory effe ct on endothelial cell proliferation and migration, and tubule formation, I n this study, we examined the antiangiogenic activity of docetaxel. Docetax el inhibited endothelial cell proliferation and tubule formation in vitro i n a dose-dependent fashion. Docetaxel treatment also inhibited angiogenesis in an in vivo Matrigel plug assay, The endothelial stimulating factors, va scular endothelial cell growth factor (VEGF) and basic fibroblast growth fa ctor are able to protect endothelial cells from the antiangiogenic properti es of docetaxel, This protective effect can be overcome by a recombinant hu manized monoclonal antibody directed against VEGF in both in vitro and in v ivo models, Similarly, combination of docetaxel with the antiangiogenic age nt 2-methoxyestradiol also overcomes the protective effect of VEGF in both in vitro and in vivo models. These data suggest that microenvironmental fac tors (e.g., local release of VEGF and basic fibroblast growth factor) could play a role in decreasing the antiangiogenic effects of docetaxel, whereas agents such as 2-methoxyestradiol and recombinant humanized monoclonal ant ibody directed against VEGF may reverse this protective effect.