Expression of multidrug resistance proteins and accumulation of cisplatin in human non-small cell lung cancer cells

被引:35
作者
Ikuta, K
Takemura, K
Sasaki, K
Kihara, M
Nishimura, M
Ueda, N
Naito, S
Lee, E
Shimizu, E
Yamauchi, A [1 ]
机构
[1] Univ Tokushima, Grad Sch Pharmaceut Sci, Tokushima 7708505, Japan
[2] Otsuka Pharmaceut Factory Inc, Div Pharmacol, Tokushima 7728601, Japan
[3] Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Pharmacol, Kobe, Hyogo 6512180, Japan
[4] Tottori Univ, Fac Med, Div Med Oncol & Mol Resp, Yonago, Tottori 6838503, Japan
关键词
multidrug resistance protein; cisplatin accumulation; non-small cell lung cancer; P-glycoprotein (MDRI); multidrug resistance-associated protein 1 (MRP1); lung resistance-related protein (LRP);
D O I
10.1248/bpb.28.707
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In order to understand and overcome multidrug resistance (MDR) of human non-small cell lung cancer (NSCLC), mRNA and protein expression levels of P-glycoprotein (MDR1), multidrug resistance-associated protein 1 (MRP1), and lung resistance-related protein (LRP) were investigated and compared with the chemosensitivity and the intracellular/intranuclear cisplatin accumulation of three NSCLC cell lines (Ma-10, Ma-31, and Ma-46). Ma-31 was more resistant than Ma-10 and Ma-46 to cisplatin, carboplatin, etoposide, and paclitaxel. The mRNA level of MDR1 was extremely low, and MDR1 protein was not detected in all cell lines. MR-P1 mRNA expression was highest in Ma-31 and lowest in Ma-10, but there was no notable difference between the MRP1 protein expression in three cell lines. LRP mRNA/protein was equally expressed in Ma-10 and Ma-31, but was nominal in Ma-46. The intracellular/intranuclear cisplatin accumulation of the cells was determined to be Ma-31 > Ma-46 > Ma-10. Thus, MDR1, MR-P1, and LRP mRNA and protein expression levels were not correlated with the chemosensitivity or the intracellular/intranuclear cisplatin accumulation of each cell line. The present results indicate that MDR proteins (MDR1, MR-P1, and LRP) may not play an important role in the chemoresistance and drug efflux of NSCLC cells.
引用
收藏
页码:707 / 712
页数:6
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