Up-Regulation of MDR1 Function and Expression by Cisplatin in LLC-PK_1 Cells

概要

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To examine whether cisplatin affects the multidrug transporter MDR1/P-glycoprotein in the kidneys, the effects of cisplatin on cell sensitivity to an anticancer drug, MDR1 function and expression were examined by assessing the growth inhibition by the MDR1 substrate paclitaxel, the uptake and efflux of the MDR1 substrate Rhodamine123 and the level of MDR1 mRNA, respectively. Porcine kidney epithelial LLC-PK_1 cells were used, as they have a structure and function similar to those of renal proximal tubular cells and physiologically express low levels of MDR1. The growth inhibitory curve of LLC-PK_1 cells by paclitaxel was shifted to a higher concentration range by pretreatment with 1μ_M cisplatin for 48h. The uptake and efflux of Rhodamine123 were significantly reduced and enhanced, respectively, by pretreatment with 1μ_M cisplatin for 48h. This enhanced efflux was suppressed by the representative MDR1 substrate/inhibitor ciclosporin. The expression of MDR1 mRNA was increased by the existence of cisplatin for 48h. These observations taken together suggested that the transient exposure to cisplatin could cause the up-regulation of MDR1 in LLC-PK_1 cells.
公益社団法人日本薬学会の論文
2003-02-01