Establishment of Drug-resistant Acute Lymphoblastic Leukemic Cell Lines and Their Resistance Mechanism

Abstract

To establish the adriamycin(ADR)-resistant ALL cell lines and to investigate their drug-resistan mechanisms. The drug-resistant cell lines SUP-B15/ADR and RS4;11/ADR were derived by exposing the parental cells [SUP-B15(Ph+) and RS4;11(Ph-)] to the ascending concentrations of ADR. The cell viability was detected by CCK-8 method. The expression of P-gp was examined by Western blot, and RT-qPCR was performed to detect the expression of MDR1. The drug-resistant cell lines SUP-B15/ADR and RS4;11/ADR were successfully established, their resistance indexes were 14.088±0.763 and 10.473±1.024, respectively. After the cryopreserved SUP-B15/ADR and RS4;11/ADR cells were resuscitated, their survival rates were 88.4±1.2% and 89.3±1.6% respectively, while their resistance indexes were 13.976±0.967 and 10.342±0.846 respectively (P>0.05). When the drug-resistant cells were cultured in the medium without ADR for 1 month, their drug-resistance indexes dropped down to 12.893±1.255 and 9.327±0.321 respectively(P<0.05). Drug-resistant cell lines had the cross-resistance to cytarabine and etoposide. The expression of P-gp and MDR1 in drug-resistant cells was significantly higher than that in wild-type cells. Two drug-resistant ALL cell lines have been successfully established by exposing to the ascending concentration of ADR. The over-expression of MDR1 and P-gp in drug-resistant cells may be one of the mechanisms underlying the drug resistance.