The Synergistic Inhibitory Effect of STI571 in Combination with Arsenic Trioxide (As_2O_3) on Multidrug-Resistant Leukemic Cells

摘要

OBJECTIVE To study the synergistic effect of STI571, an inhibitor of tyrosine kinase, in combination with arsenic trioxide As_2O_3 on a multidrug-resistant leukemia cell line expressing bcr-abl. METHODS The cytotoxic effect of STI571 alone or in combination with different concentrations of As_2O_3 on the bcr-abl and mdr1 -positive leukemia cell line, K562-n/VCR, was examined by the MTT method. RESULTS One μmol/L of STI571 alone had no significant cytotoxic effect on K562-n/VCR cells. However the cytotoxic effect increased markedly when combined with As_2O_3 at concentrations of 10~(-5), 10~(-6), 10~(-7) and 10~(-8) mol/L. The IC_(50) of K562-n/VCR cells in As_2O_3 group was 1.879 μmol/L, with Upon addition of STI571, the IC_(50) decreased to 0.155 μmol/L resulting in a synergistic cytotoxic effect on K562-n/VCR cells that was increased 12.1 times. CONCLUSION A combination of STI571 with As_2O_3 has a more powerful inhibitory effect on leukemia cells expressing positive bcr-abl and positive mdrl compared to the effect with As_2O_3 alone.