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

Christopher J. Sweeney, Kathy D. Miller, Sean E. Sissons, Shinichi Nozaki, Douglas K. Heilman, Jianzhao Shen, George W. Sledge

Research output: Contribution to journalArticle

303 Scopus citations

Abstract

Numerous chemotherapeutic agents have been shown to have an inhibitory effect on endothelial cell proliferation and migration, and tubule formation. In this study, we examined the antiangiogenic activity of docetaxel. Docetaxel inhibited endothelial cell proliferation and tubule formation in vitro in a dose-dependent fashion. Docetaxel treatment also inhibited angiogenesis in an in vivo Matrigel plug assay. The endothelial stimulating factors, vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor are able to protect endothelial cells from the antiangiogenic properties of docetaxel. This protective effect can be overcome by a recombinant humanized monoclonal antibody directed against VEGF in both in vitro and in vivo models. Similarly, combination of docetaxel with the antiangiogenic agent 2-methoxyestradiol also overcomes the protective effect of VEGF in both in vitro and in vivo models. These data suggest that microenvironmental factors (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 antibody directed against VEGF may reverse this protective effect.

Original languageEnglish (US)
Pages (from-to)3369-3372
Number of pages4
JournalCancer Research
Volume61
Issue number8
StatePublished - Apr 15 2001

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this