Inhibitory effect of STI571 in combination with chemotheraputic drug on a multi-drug resistant leukemia cell line expressing bcr-abl / 中国癌症杂志

ABSTRACT

Purpose: To study new treatment of leukemia with both bcr-abl and mdrl positive. Methods: We detected the effect of STI571 ( 1 ?mol/L), an inhibitor of tyrosine kinase, in combination respectively with vincristine (VCR), daunorubicin (DNR), homoharringtonin( HHT) ( 10-4,10-5, 10-6, 10-7,10-8 mol/L) and DNR + arabinoside cytosine (Ara-C) of 1 mmol/L on a high tumorigenicity in nude mice multi drug-resistant leukemia cell line ( K562-n/VCR) by MTT method. Results: IC50 of VCR and VCR + STI571 were 127.28 ?mol/L, 1. 37 ?mol/L respectively, and synergistic interaction on K562-n/VCR cells was 93. 04-fold. IC50 of DNR and DNR + STI571 were 6. 96?mol/L, 0. 30?mol/L respectively, synergistic interaction was 23. 35-fold. IC50 of HHT and HHT + STI571 were 156.70?mol/L, 7.916?mol/L respectively, synergistic interaction was 19. 80-fold. IC50 of DNR + Ara-C and DNR + Ara-C + STI571 were 0. 10 ?mol/L, 0. 015 ?mol/L respectively, the synergistic interaction was 464-fold. Chemotheraputic agents have not intensive cytotoxic effect on K562-n/VCR cells, but the cytotoxic effect became greater when combined with STI571. Conclusions: Combination of STI571 with DNR, VCR, HHT and DNR + Ara-C had a greater synergistic inhibiting effect on K562-n/ VCR cells . The combinations of STI571 and these Chemotheraputic agents would display synergistic activity in bcr-abl and mdrl positive leukemia cells.