文献类型：期刊文献

英文题名：Modulation of P-glycoprotein function and reversal of multidrug resistance by (-)-epigallocatechin gallate in human cancer cells

作者：Qian, F; Wei, DZ; Zhang, Q; Yang, SL

机构：[1]E China Univ Chem Technol, New World Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2005

卷号：59

期号：3

起止页码：64

外文期刊名：BIOMEDICINE & PHARMACOTHERAPY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000228680300002)】；

语种：英文

外文关键词：(-)-epigallocatechin gallate; multidrug resistance; P-glycoprotein

摘要：Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. In this study, the reversal of P-glycoprotein (P-gp) mediated multidrug resistance by (-)-epigallocatechin gallate (EGCG) and its molecular mechanism were investigated. A three-dimensional model of carboxyl-terminal nucleotide binding domain (NBD2) from P-gp was built by homology modeling. The structural model of the complex indicates that EGCG was tightly bound to the ATP-binding site of NBD2. EGCG modulated the function of P-gp and increased the intracellular accumulation of chemotherapeutic agent doxorubicin (DOX) in drug-resistant KB-A1 cells. When KB-A1 cells were exposed to 10 mu g/ml DOX combined with 10, 30, 50 mu M EGCG for 4 h, the intracellular concentrations of DOX were increased 1.5, 1.9, 2.3 times, respectively compared with DOX alone treatment. In vitro EGCG potentiated the cytotoxicity of DOX to drug-resistant KB-A1 cells. In KB-A1 cell xenograft model, EGCG could also enhance the efficacy of DOX and increased the DOX concentration in the resistant tumors. Thus, these results suggest that EGCG modulated the function of P-gp and reversed P-gp mediated multidrug resistance in human cancer cells. (c) 2005 Elsevier SAS. All rights reserved.