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.
Laboratoire d'Hématologie et d'Hémostase, Institut Jean-Godinot, Reims, France.
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Mouchard-Delmas
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Devie-Hubert
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Dufer
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D013925:Thromboplastin; D013917:Thrombin; D000077235:Vinorelbine