Oxaliplatin up-regulated the function and expression of P-glycoprotein/MDR1 in porcine kidney epithelial LLC-PK cells

Kishi, Hisato; Kitada, Noriaki; Ohnishi, Noriaki; Sakaeda, Toshiyuki; Takara, Kohji; Yokoyama, Teruyoshi

Oxaliplatin up-regulated the function and expression of P-glycoprotein/MDR1 in porcine kidney epithelial LLC-PK cells

dc.contributor.author	Kishi, Hisato	de
dc.contributor.author	Kitada, Noriaki	de
dc.contributor.author	Ohnishi, Noriaki	de
dc.contributor.author	Sakaeda, Toshiyuki	de
dc.contributor.author	Takara, Kohji	de
dc.contributor.author	Yokoyama, Teruyoshi	de
dc.date.accessioned	2008-06-17T14:02:57Z
dc.date.available	2008-06-17T14:02:57Z
dc.date.issued	2006-10-26	de
dc.description.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.	en
dc.identifier.issn	1611-2156	de
dc.identifier.uri	http://hdl.handle.net/2003/25660
dc.identifier.uri	http://dx.doi.org/10.17877/DE290R-8185
dc.language.iso	en	de
dc.relation.ispartofseries	EXCLI Journal ; Vol. 5, 2006	en
dc.subject	LLC-PK	en
dc.subject	MDR1	en
dc.subject	oxaliplatin	en
dc.subject	P-glycoprotein	en
dc.subject	up-regulation	en
dc.subject.ddc	610
dc.title	Oxaliplatin up-regulated the function and expression of P-glycoprotein/MDR1 in porcine kidney epithelial LLC-PK cells	en
dc.type	Text	de
dc.type.publicationtype	article	de
dcterms.accessRights	open access
eldorado.dnb.zdberstkatid	2132560-1

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