Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T
Department of Agricultural Chemistry, Faculty of Agriculture, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
FEBS Lett. 1993 Jun 7;324(1):99-102. doi: 10.1016/0014-5793(93)81540-g.
Understanding of the interactions between P-glycoprotein and multidrug resistance (MDR) reversing agents is important in designing more effective MDR modulators. We examined transcellular transport of several MDR 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 azidopine and diltiazem across the LLC-GA5-COL300 monolayer were increased and apical-to-basal transports were decreased compared to those across the LLC-PK1 monolayer, indicating that P-glycoprotein transports azidopine and diltiazem. Movements of nitrendipine and staurosporine across the epithelial monolayer were not affected by P-glycoprotein. These results suggests that some MDR modulators exert their inhibitory effect not only by blocking the initial binding of anticancer drugs but throughout the course of the transport process.
了解P-糖蛋白与多药耐药（MDR）逆转剂之间的相互作用对于设计更有效的MDR调节剂很重要。我们使用药物敏感的上皮细胞系LLC-PK1及其在顶端表面表达人P-糖蛋白的转化细胞系LLC-GA5-COL300，研究了几种MDR调节剂的跨细胞转运。与通过LLC-PK1单层的转运相比，叠氮平与地尔硫卓通过LLC-GA5-COL300单层的基底到顶端转运增加，顶端到基底转运减少，表明P-糖蛋白转运叠氮平和地尔硫卓。尼群地平和星形孢菌素通过上皮单层的转运不受P-糖蛋白的影响。这些结果表明，一些MDR调节剂不仅通过阻断抗癌药物的初始结合，而且在整个转运过程中发挥其抑制作用。
