四川大学学报（医学版）2012，Vol.43Issue(5)：657-660,665,5.
多药耐药基因MDR1在Ph(+)急性淋巴细胞白血病伊马替尼耐药细胞株SUP-B15/RI耐药形成中的作用
Multidrug Resistant Gene MDR1 Contributes to Development of Imatinib-Resistance in Ph (+)Acute Lymphoblastic Leukemia Cell Line SUP-B15RI
摘要
Abstract
Objective To investigate the contribution of multidrug-resistant gene MDRl to development of imatinib-resistance in Ph( + )acute lymphoblastic leukemia cell line SUP-B15/RI. Methods RT-PCR was used to examine MDRl 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 MDRl 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 (Z0. 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. Conclusion The overexpression of MDRl 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.关键词
伊马替尼耐药/MDR1/P-gp/SUP-B15细胞株/Ph(+)急性淋巴细胞白血病Key words
Imatinib resistance/MDRl/P-gp/SUP-B15 cell line/Ph(+)acute lymphoblastic/leukemia引用本文复制引用
林娟,邢宏运,龚玉萍,杨曦,郭勇,单卿卿,周睿卿..多药耐药基因MDR1在Ph(+)急性淋巴细胞白血病伊马替尼耐药细胞株SUP-B15/RI耐药形成中的作用[J].四川大学学报（医学版）,2012,43(5):657-660,665,5.基金项目
国家自然科学基金(No.30770912)、四川省科技厅社会公益项目(No.2008SZ0017)和教育部回国留学人员启动金(No.20071108-18-4)资助 （No.30770912）
