P-GLYCOPROTEIN-MEDIATED TRANSCELLULAR TRANSPORT OF MDR-REVERSING AGENTS

Understanding of the interactions between P-glycoprotein and multidrug resistance (MDR) reversing agents is important in designing more effe ctive MDR modulators. We examined transcellular transport of several M DR modulators by using a drug-sensitive epithelial cell line, LLC-PK1. and its transformant cell line, LLC-GA5-COL300, which expresses human P-glycoprotein on the apical surface. Basal-to-apical transports of a zidopine and diltiazem across the LLC-GA5-COL300 monolayer were increa sed and apical-to-basal transports were decreased compared to those ac ross the LLC-PK1 monolayer, indicating that P-glycoprotein transports azidopine and diltiazem. Movements of nitrendipine and staurosporine a cross the epithelial monolayer were not affected by P-glycoprotein. Th ese results suggests that some MDR modulators exert their inhibitory e ffect not only by blocking the initial binding of anticancer drugs but throughout the course of the transport process.