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.