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《Journal of Sichuan University(Medical Science Edition)》 2010-06
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Effect and Mechanism of DNMT Inhibitor on the Reversal of Multidrug Resistance in Human Colon Cancer Cell Line sw620/L-OHP

DENG Qian1,LI Zhi-ping1,HUANG Chun-mei1,LIU Zhen1,ZHONG Ren-ming2,LI Ai-jun2,BI Feng3,TANG Qiu-lin3.1.Abdominal Oncology Department,West China Hospital,Sichuan University,Chengdu 610041,China;2.Oncology Radiation Therapy Centre,West China Hospital,Sichuan University,Chengdu 610041,China;3.Laboratory of Signal Transduction and Molecular Targeting Therapy,West China Hospital,Sichuan University,Chengdu 610041,China  
Objective To explore whether demethylation inhibitor 5-aza-2'-deoxycytidine(5-aza-dC) could reverse multidrug resistacne(MDR) of human colon cancer and its impacts on the expressions of Bcl-2/adenovirus E1B 19 KDa protein interacting protein 3(BNIP3),P-glycoprotein(P-GP) and multidrug resistanceassociated protein(MRP),as well as the activity of DNA methyltransferase(DNMT).Methods Oxaliplatin(L-OHP) resistant human colon carcinoma cells(sw620/L-OHP) and its parental cells(sw620) were used to determine the effect of 5-aza-dC.CCK-8 assay was adopted to evaluate the cytotoxicity of 5-aza-dC.Western blot was performed to observe the expressions of BNIP3,P-GP and MRP.3H microassay was used to detect the activity of DNMT.Results After the addition of 1.4 μmol/L 5-aza-dC, the 50% inhibitory concentration(IC50) of L-OHP to sw620/L-OHP cells was decreased from(0.335±0.043) μg/mL to(0.069±0.023) μg/mL,and the chemosensitivity increased 8.26 times(P0.001).Western blot analysis showed that the expression of BNIP3 was up-regulated by 5-aza-dC in a concentration-dependent manner(P0.001),and P-GP and MRP expression were also significantly changed(P0.05) but not in a concentration-dependent manner(P0.05).DNMT activity was down-rugulated by 5-aza-dC in sw620/L-OHP cells (P0.001).Conclusions 5-aza-dC could reversed multi drug resistance of sw620/L-OHP,which may due to the demethylation to upregulate BNIP3 expression,and inhibite the expression of resistance-associated protein P-GP and MRP furtherly by some unknown mechanism.
【CateGory Index】: R735.3
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【Citations】
Chinese Journal Full-text Database 1 Hits
1 BAI Zhi Yong 1, XU Guo Bin 2, WU Shu Lan 1 (1. Department of Hematology, 2. Department of Laboratory, the First Hospital, Beijing Medical University, Beijing 100034, China);Detection of DNA-methyltransferase activity of leukemia cells with radiology microassay[J];Journal of Beijing Medical University;2000-01
【Co-citations】
Chinese Journal Full-text Database 5 Hits
1 BAI Xiao-chuan,BAI Zhi-yong,WU Shu-lan * Department of Hematology,the First Teaching Hospital ,Beijing Medical University,Beijin g 100034,P.R.China;Relationship between the Pattern of Methylation of Calcitonin Gene and Activity of Methyltransferase in 8Tumor Cell Lines[J];Chinese Journal of Cancer;2001-02
2 ZHAO Ming Ming 1, BAI Zhi Yong 1, BAI Xiao Chuan 1, XU Guo Bin 2, WU Shu Lan 1 (1.Department of Hematology, 2. Department of Laboratory Medical Science, the First Hospital, Beijing Medical University, Beijing 100034, China);Study on the mechanism of the hypermethylation of the calcitonin gene in HL-60 cells[J];Journal of Beijing Medical University;2000-06
3 LU Jia you, BIAN Xiu wu, ZHAO Wen, XU Cheng ping, JIANG Xue feng (Institute of Pathology, Southwest Hospital , Third Military Medical University, Chongqing 400038, China);Changes of DNA methylation during differentiation of human glioma cells induced by NDGA[J];Acta Academiae Medicinae Militaris Tertiae;2003-04
4 ;Epigenetic regulation for prevention and gene therapy of tumors[J];Journal of Xinxiang Medical College;2004-06
5 CHEN Hua,WU Shu-Lan,ZHU Qiang,SHI Yong-Jin,XU Guo-Bin,WANG Jian-Zhong (Department of Hematology,The First Hospital of Peking University,Department of Laboratory,The First Hospital of Peking University,Beijing 100034);Inhibitory Effect on Proliferation of KG1a Cell Line by Methyltransferase Inhibitors[J];Journal of Experimental Hematology;2002-04
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