title: [Multidrug resistant gene MDR1 contributes to development of imatinib-resistance in Ph (+) acute lymphoblastic leukemia cell line SUP-BS15RI].
abstract: OBJECTIVE
  To investigate the contribution of multidrug-resistant gene MDR1 to development of imatinib-resistance in Ph(+) acute lymphoblastic leukemia cell line SUP-B15/RI.
  
  
  METHODS
  RT-PCR was used to examine MDR1 mRNA levels, cytotoxic effects of imatinib (IM), daunorubicin (DNR), vincristine (VCR), etoposide (VP-16) and the synergetic antiproliferation with P-gp inhibitor verapamil on sensitive SUP-B15 and SUP-B15/RI cell lines were detected by the MTT assay. The P-gp function was measured by flow cytometry.
  
  
  RESULTS
  Increased expression of MDR1 gene in SUP-B15/RI than that of SUP-B15 cell line (P < 0.05) was observed when detected with RT-PCR. The IC50 values of SUP-B15/RI cell line inhibited by IM, DNR, VCR, VP-16 for 72 hours was higher than that of SUP-B15 (P < 0.05) and the resistant factor (RF) was (20.52 +/- 2.34), (10.33 +/- 1.88), (9.78 +/- 1.27), (3.84 +/- 0.69) respectively. The IC50 values of IM, DNR, VCR, VP-16 combined with P-gp inhibitor verapamil were decreased in SUP-B15/RI cells (P < 0.05), reversal of drug resistance was (1.44 +/- 0.43), (3.20 +/- 0.17), (1.44 +/- 0.12), (1.33 +/- 0.14) respectively. The activity of P-gp in SUP-B15/RI measured by flow cytometry was higher than that of P-gp in SUP-B15/RI cell line.
  
  
  CONCLUSIONS
  The overexpression of MDR1 mRNA and higher activity of P-gp is partially responsible for acquiring of imatinib resistance in SUP-B15/RI cell line. P-gp inhibitor verapamail can partially restored the sensitivity of the SUP-B15/RI cell line to anticancer agents.
authors.affiliation: Department of Hematology and Research Lab of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lin
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Xing
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Gong
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Shan
authors.forename: Rui-Qing
authors.initials: RQ
authors.lastname: Zhou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
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; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate