Authors: | Kishi, Hisato Kitada, Noriaki Ohnishi, Noriaki Sakaeda, Toshiyuki Takara, Kohji Yokoyama, Teruyoshi |
Title: | Oxaliplatin up-regulated the function and expression of P-glycoprotein/MDR1 in porcine kidney epithelial LLC-PK cells |
Language (ISO): | en |
Abstract: | The purpose of this study was to clarify the effects of oxaliplatin on the function and expression of the multidrug efflux transporter P-glycoprotein/MDR1 in a porcine kidney epithelial cell line, LLC-PK, as a renal tubular epithelial model. LLC-PK cells were pretreated with or without oxaliplatin for 48 h, and the growth inhibitory effects of a MDR1 substrate, paclitaxel, and the transport of a MDR1 substrate, Rhodamine123, were assessed. The level of MDR1 mRNA and protein was also examined in the cells treated with or without oxaliplatin for 48 h using RT-PCR and immunoblotting. In the present study, the pretreatment with oxaliplatin tended to suppress the growth inhibitory effects of paclitaxel in LLC-PK cells, presumably by accelerating the functions of MDR1. In addition, the uptake of Rhodamine123 was reduced significantly by pretreatment with oxaliplatin, and the efflux of Rhodamine123 from LLC-PK cells was enhanced significantly. These accelerated functions were supported by the suppression of Rhodamine123 s transport by a representative MDR1 substrate/inhibitor, ciclosporin, at 10 µM. The exposure to oxaliplatin for 48 h resulted in an increase in the expression of MDR1 in LLC-PK cells. These findings were similar to those obtained with cisplatin, a nephrotoxic drug. In conclusion, the present findings suggested that transient exposure for 48 h to oxaliplatin caused the up-regulation of MDR1 function and expression in LLC-PK cells, as was the case for cisplatin. |
Subject Headings: | LLC-PK MDR1 oxaliplatin P-glycoprotein up-regulation |
URI: | http://hdl.handle.net/2003/25660 http://dx.doi.org/10.17877/DE290R-8185 |
Issue Date: | 2006-10-26 |
Appears in Collections: | Original Articles |
Files in This Item:
File | Description | Size | Format | |
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Takara18-06proofrev.pdf | DNB | 259.51 kB | Adobe PDF | View/Open |
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