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.