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Effects of Platinum Derivatives on the Function and Expression of P-Glycoprotein/MDR1 in LLC-PK1 Cells: In the Cases of Carboplatin and Nedaplatin

Author(s): Noriaki Kitada | Kohji Takara | Masayuki Tsujimoto | Toshiyuki Sakaeda | Noriaki Ohnishi | Teruyoshi Yokoyama

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 3;
Issue: 1;
Start page: 23;
Date: 2007;
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Keywords: MDR1 | carboplatin | nedaplatin | LLC-PK1 cell

AIM: The aim of this study is to investigate the effects of carboplatin and nedaplatin on the function and expression of P-glycoprotein/MDR1 using porcine kidney epithelial LLC-PK1 cells, and to compare their characteristics with cisplatin or oxaliplatin. METHODS: The transport activity of MDR1 was examined in LLC-PK1 and MDR1-overexpressing Hvr100-6 cells. The expression level of MDR1 was analyzed with RT-PCR and immunoblotting analyses. RESULTS: Neither carboplatin nor nedaplatin affected the accumulation of Rhodamin123 in Hvr100-6 cells, suggesting that both drugs were not the substrates for MDR1. In addition, LLC-PK1 cells treated for 48 h with 1 micromolar carboplatin did not exhibit any change in subsequent Rhodamine123 transport. Cellular MDR1 mRNA and protein expression was also not altered by carboplatin. In the case of nedaplatin, the accumulation of Rhodamine123 was significantly decreased when LLC-PK1 cells were pre-treated with 1 micromolar of nedaplatin for 48 h, although nedaplatin did not affect the efflux of Rhodamine123. Nedaplatin did not up-regulate both mRNA and protein levels of MDR1. CONCLUSION: Unlike cisplatin and oxaliplatin to induce MDR1, carboplatin and nedaplatin did not affect the function and expression of MDR1 in LLC-PK1 cells.
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