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Involvement of P-glycoprotein in an in vitro blood-brain barrier model

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The P-glycoprotein (P-gp) multidrug transporter is present at the luminal face of the brain capillary endothelial cells that contribute to the blood-brain barrier. To study its role in transendothelial anticancer drug transport, we made use of a co-culture system formed of bovine brain capillary endothelial cells and astrocytes which allows the in vitro maintenance of specialized properties of the brain endothelial cells, including expression of P-gp as assessed by Northern and Western blot analyses. Vinblastine, an anticancer drug substrate for P-gp and known not to enter the brain, was found to be poorly transferred across the endothelial cell monolayer. This low vinblastine transport was however strongly increased in the presence of verapamil, a well known P-gp blocker. Moreover, verapamil was shown to increase the accumulation of the anticancer drug in the brain endothelial cells through inhibition of drug efflux. These results suggest that P-gp activity evidenced in the co-culture model is involved in the low transendothelial transport of vinblastine, thus supporting the conclusion that P-gp expressed at the blood-brain barrier level may prevent xenobiotics, including anticancer drugs, from entering the central nervous system.
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Document Type: Research Article

Affiliations: FAC PHARM,GRP DETOXICAT & REPARAT TISSULAIRE,F-35043 RENNES,FRANCE. INST RECH PIERRE FABRE,F-81100 CASTRES,FRANCE.

Publication date: November 1, 1996

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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