Show simple item record

dc.contributor.authorYan, Fengzh_CN
dc.contributor.authorWang, Xiao-Minzh_CN
dc.contributor.authorPan, Chaozh_CN
dc.contributor.authorMa, Quan-Mingzh_CN
dc.contributor.author王效民zh_CN
dc.contributor.author潘超zh_CN
dc.date.accessioned2015-07-22T07:36:29Z
dc.date.available2015-07-22T07:36:29Z
dc.date.issued2009-03-28zh_CN
dc.identifier.citationWORLD JOURNAL OF GASTROENTEROLOGY, 2009,15(12):1443-1451zh_CN
dc.identifier.otherWOS:000264711700006zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/93164
dc.descriptionInnovation Fund of Fujian Province [2007-CXB-7]; Key Science and Technology Project of Xiamen [3502Z20077045]zh_CN
dc.description.abstractAIM: 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.zh_CN
dc.language.isoen_USzh_CN
dc.publisherWORLD J GASTROENTEROzh_CN
dc.source.urihttp://dx.doi.org/10.3748/wjg.15.1443zh_CN
dc.subjectDRUG-RESISTANCEzh_CN
dc.subjectCANCER-CELLSzh_CN
dc.subjectPROTEINzh_CN
dc.subjectREVERSALzh_CN
dc.subjectPATHWAYSzh_CN
dc.subjectINHIBITIONzh_CN
dc.subjectEXPRESSIONzh_CN
dc.subjectCHEMORESISTANCEzh_CN
dc.subjectMODULATIONzh_CN
dc.subjectADRIAMYCINzh_CN
dc.titleDown-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cellszh_CN
dc.typeArticlezh_CN


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record