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In Vitro and In Vivo Inhibition of MRP Gene Expression and Reversal of Multidrug Resistance by siRNA
Author(s) -
Wu Zhuo,
Li Xiaobo,
Zeng Yanyan,
Zhuang Xiaoming,
Shen Hong,
Zhu Haiqing,
Liu Hongyi,
Xiao Hong
Publication year - 2011
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2010.00642.x
Subject(s) - multiple drug resistance , in vivo , efflux , rna interference , gene silencing , small interfering rna , in vitro , drug resistance , biology , pharmacology , gene expression , cancer research , chemistry , transfection , gene , rna , biochemistry , microbiology and biotechnology , genetics
Clinical drug resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. One mechanism by which a living cell can achieve multidrug resistance (MDR) is via the active efflux of a broad range of anti‐cancer drugs through the cellular membrane by MDR proteins. Over‐expression of multidrug resistance‐associated protein 1 (MRP1) is one of the important MDR phenotypes. RNA interference (RNAi) is a fundamental cellular mechanism for silencing gene expression that can be harnessed for the development of new drugs. In our study, by using lipofectamin TM 2000 (Invitrogen, Carlsbad, CA, USA) in vitro and electric pulse in vivo to delivery siRNA, we successfully inhibited MRP1 both at mRNA and protein level as determined by reverse transcription‐PCR and western blot or immunohistochemistry. Furthermore, the efficacy of chemotherapeutic drugs (epirubicin) to tumour cells dramatically improved both in vivo and in vitro . These studies demonstrate that through efficient delivery siRNA, MRP1‐mediated MDR can be reversed and siRNA can be used for further study in clinical cancer therapy.