title: Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells.
abstract: The multidrug resistance (MDR) mediated by P-glycoprotein (P-gp), the MDR1 gene product, is one of the major obstacles in leukemia treatment. The present study was designed to explore a MDR1-targeted small interfering RNA (si-MDR1) approach for reversal of P-gp-mediated MDR in the MDR human leukemia cell line k562/A02. It was found that si-MDR1 significantly inhibited MDR1 expression at both mRNA and protein levels. Depletion of MDR1 by si-MDR1 correlated with the increased sensitivity of the cells to cytotoxic agents and with the enhanced intracellular retention of daunorubicin (DNR). One base-pair mutated control (si-MDR1-Mut) lost the effect of si-MDR1 on both the degradation of mdr1 mRNA and the reduction of P-gp expression. These findings indicate that siRNA specifically and efficiently interferes with the expression of mdr1 and could be used as a molecularly defined therapeutic approach for MDR in the treatment of leukemia.
authors.affiliation: The Faculty of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Peng
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xiao
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Cai
authors.forename: Shihong
authors.initials: S
authors.lastname: Lu
authors.forename: Wenli
authors.initials: W
authors.lastname: Feng
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D034741:RNA, Small Interfering; D003630:Daunorubicin