title: In vitro and in vivo inhibition of MRP gene expression and reversal of multidrug resistance by siRNA.
abstract: 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.
authors.affiliation: Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhuang
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zhu
authors.forename: Hongyi
authors.initials: H
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D018274:Electroporation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008055:Lipids; D008297:Male; D051379:Mice; D008819:Mice, Nude; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C086724:Lipofectamine; C421109:multidrug resistance-associated protein 1