J. Cancer Mol. 3: 23-28, 2007
[Research Paper]
Effects of Platinum Derivatives on the Function and Expression of
P-Glycoprotein/MDR1 in LLC-PK1 Cells: In the Cases of
Carboplatin and Nedaplatin
Noriaki Kitada, Kohji Takara1, Masayuki Tsujimoto,
Toshiyuki Sakaeda, Noriaki Ohnishi, and Teruyoshi Yokoyama
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences,
Kyoto Pharmaceutical University, Kyoto, Japan [N. Kitada, K. Takara,
M. Tsujimoto, N. Ohnishi, T. Yokoyama] and Department of Hospital
Pharmacy, School of Medicine, Kobe University, Kobe, Japan [T. Sakaeda]
Abstract:
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
microM
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
microM
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.
(Keywords: MDR1;
carboplatin; nedaplatin; LLC-PK1 cell)
___________________________________________________________________________________
Received 12/25/06; Revised 1/21/07; Accepted 1/22/07.
1Correspondence:
Dr. Kohji Takara, Department of Hospital Pharmacy, Faculty of
Pharmaceutical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Phone:
81-75-595 4628. Fax: 81-75-595 4752. E-mail:
takara@mb.kyoto-phu.ac.jp
2Abbreviations:
MDR, multidrug resistance; IC50, 50% growth inhibitory
concentration; HBSS,
Hanksˇ¦ balanced salt solution; CsA, ciclosporin A;
WST-1, 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium,
monosodium salt;
1-methoxy PMS, 1-methoxy-5-methylphenazinium methylsulfate; BA, beta-actin; PBS-T,
PBS containing 0.1% Tween 20; HRP, horseradish peroxidase; ClogP, calculated logarithmic value of the n-octanol/water
partition coefficient.
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