title: Lentivirus-mediated RNA interference reversing the drug-resistance in MDR1 single-factor resistant cell line K562/MDR1.
abstract: Multidrug-resistance (MDR) is a major hindrance to successful chemotherapy. The emergence of MDR is multi-factorial. Among them, the MDR1 gene/P-glycoprotein (P-gp) is a popular and important reason. In our study, an MDR1 single-factorial drug-resistant leukemia cell line K562/MDR1 was constructed via transferring full-length human MDR1 cDNA into drug-sensitive K562 cells. The short-hairpin RNA (shRNA) targeting MDR1 gene was transfected into K562/MDR1 cell lines by the replication-defective lentiviral vector derived from HIV-1. The efficiency of RNA interference (RNAi) to silence the MDR1 gene and reverse multidrug-resistance in the MDR1 single-factor drug-resistance cell line K562/MDR1 was evaluated. The multi-factor resistant cell line K562/A02, induced by doxorubicin exposure, was used as a control. After RNA interference, the expression of the MDR1 gene and P-gp in K562/MDR1 was markedly down-regulated and the drug sensitivity was restored as IC(50) values became similar to the K562 sensitive cell line. The expression of the MDR1 gene and P-gp in K562/A02 was markedly down-regulated too, and drug-resistance to anticancer drug is reduced to some extent but the IC(50) was significantly higher than that of the sensitive cell line. These results demonstrated that lentivirus-mediated RNAi could efficiently down-regulate the expression of MDR1 and Pgp, and successfully reverse a cell's resistance to chemotherapeutic. Due to only MDR1 resistance, the K562/MDR1 cell showed much high specificity and thus is a better cell model for MDR1/P-gp research.
authors.affiliation: Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan Province, China.
authors.forename: Xueshi
authors.initials: X
authors.lastname: Ye
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Yuping
authors.initials: Y
authors.lastname: Gong
authors.forename: Bohui
authors.initials: B
authors.lastname: Zheng
authors.forename: Wentong
authors.initials: W
authors.lastname: Meng
authors.forename: Yamei
authors.initials: Y
authors.lastname: Leng
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005822:Genetic Vectors; D015497:HIV-1; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D034622:RNA Interference
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin