Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

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	Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells
	Yan, Feng ; Wang, Xiao-Min ; Pan, Chao ; Ma, Quan-Ming ; Wang XM(王效民) ; Pan C(潘超)
刊名	http://dx.doi.org/10.3748/wjg.15.1443
	2009-03-28
关键词	DRUG-RESISTANCE CANCER-CELLS PROTEIN REVERSAL PATHWAYS INHIBITION EXPRESSION CHEMORESISTANCE MODULATION ADRIAMYCIN
英文摘要	Innovation Fund of Fujian Province [2007-CXB-7]; Key Science and Technology Project of Xiamen [3502Z20077045]; AIM: To study the expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1 and ERK2 in multidrug resistant (MDR) hepatocellular carcinoma (HCC) cells. METHODS: MDR HCC cell lines, HepG2/adriamycin (ADM) and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein (P-gp) and multidrug resistant protein I (MRP1) expression levels. ERK1 and ERK2 mRNA expression levels were measured by quantitative real-time PCR (QRT-PCR). Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot. RESULTS: MTT assay showed that HepG2/ADM and SMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells (8.92% +/- 0.22% vs 0.88% +/- 0.05%, P < 0.001) and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells (7.37% +/- 0.26% vs 1.74% +/- 0.25%, P < 0.001). However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells. CONCLUSION: ERK1 and ERK2 activities are down-regulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells. (C) 2009 The WJG Press and Baishideng. All rights reserved.
语种	英语
出版者	WORLD J GASTROENTERO
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93164]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Yan, Feng,Wang, Xiao-Min,Pan, Chao,et al. Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells[J]. http://dx.doi.org/10.3748/wjg.15.1443,2009.
APA	Yan, Feng,Wang, Xiao-Min,Pan, Chao,Ma, Quan-Ming,王效民,&潘超.(2009).Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells.http://dx.doi.org/10.3748/wjg.15.1443.
MLA	Yan, Feng,et al."Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells".http://dx.doi.org/10.3748/wjg.15.1443 (2009).