Multidrug Resistant Gene MDR1 Contributes to Development of Imatinib-Resistance in Ph(+) Acute Lymphoblastic Leukemia Cell Line SUP-B15RI

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. Conclusion 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.