THE MICROTUBULE-AFFECTING DRUG PACLITAXEL HAS ANTIANGIOGENIC ACTIVITY

Endothelial cell migration is a critical event during angiogenesis, an d inhibitors of cell motility can affect the angiogenic process, Pacli taxel (Taxol(R)), a microtubule-stabilizing antineoplastic cytotoxic d rug, inhibits motility and invasiveness of several cell types, The aim of this study was to investigate the effect of paclitaxel on endothel ial cell functions and on angiogenesis, in vivo, paclitaxel (20-28 mg/ kg i.v.) significantly inhibited the angiogenic response induced by tu mor cell supernatant embedded in a pellet of reconstituted basement me mbrane (Matrigel) injected s.c. into C57BL/6N mice, In vitro, paclitax el inhibited endothelial cell proliferation, motility, invasiveness, a nd cord formation on Matrigel in a dose-dependent manner, The antiangi ogenic activity of paclitaxel was not linked to its cytotoxicity, sinc e inhibition of endothelial cell chemotaxis and invasiveness occurred at drug concentrations which did not affect endothelial cell prolifera tion, Another cytotoxic drug, cisplatin, that inhibited endothelial ce ll proliferation irt vitro, did not affect angiogenesis in vivo, These data indicate that paclitaxel has a strong antiangiogenic activity, a property that might contribute to its antineoplastic activity in vivo .