Effects of the Anticancer Agent Vinorelbine on Endothelial Cell Permeability and Tissue-factor Production in Man

Because antineoplastic drugs could increase endothelial blood barrier permeability and thrombotic diseases have been described as a complication of treatments with vinca alkaloids, the effect of a therapeutic dose (10‐8 M) of vinorelbine on transendothelial permeability was analysed by measuring the movement of albumin across a monolayer of human venous endothelial cells. Induction of procoagulant activity was assessed by evaluation of tissue‐factor activity in cell lysates. Vinorelbine increased the permeability of endothelial cells after 3 h of culture, as observed with thrombin. In addition, thrombin induced strong tissue‐factor activity, a phenomenon not observed after vinorelbine treatment. These data suggest that vinorelbine could modulate endothelial barrier permeability. This effect is not linked to an increase in tissue‐factor activity, suggesting that their induction could operate through separate pathways.