title: Specific reversal of MDR1/P-gp-dependent multidrug resistance by RNA interference in colon cancer cells.
abstract: No control cell line was available for previous RNA interference studies on reversal of multidrug resistance (MDR) in colon cancer cells. Here, human COLO 320DM, with HT-29 as the control, colon cancer cell lines were used to investigate the reversal of MDR1/P-gp-dependent MDR by siRNA (#4123 and #4029 MDR1 siRNAs) targeting to MDR1 mRNA. Both siRNAs inhibited expression of MDR1 and P-gp in COLO 320DM. The minimum inhibition concentrations were 5 nmol/l of #4123 and 25 nmol/l of #4029. #4123 MDR1 siRNA took effect in 4, 5 and 6 days at doses of 5, 25 and 100 nmol/l, respectively. Increased cytotoxicity of the antitumor drugs adriamycin and vincristine with increased intracellular adriamycin accumulation accompanied inhibition of MDR1 mRNA and P-gp expression. No such effects were found in the HT-29 control. MDR1 siRNAs specifically reversed the MDR of colon cancer cells demonstrating a possible new approach for treating MDR1/P-gp-dependent multidrug resistance.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, P.R. China. xiazhsh@hotmail.com
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Xia
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Zhu
authors.forename: Liyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Crista
authors.initials: C
authors.lastname: Royal
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.forename: Qikui
authors.initials: Q
authors.lastname: Chen
authors.forename: Bao-Ling
authors.initials: BL
authors.lastname: Adam
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism* / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014750:Vincristine / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D014750:Vincristine; D004317:Doxorubicin; C022616:thiazolyl blue