Effect of low-dose decitabine in combination with imatinib mesylate in K562 cells / 白血病·淋巴瘤

ABSTRACT

Objective Imatinib mesylate (IM) is the most active agent in treating chronic myeloid leukemia (CML). 5-Aza-2-deoxycytidine (DAC) is a cytosine analogue that inhibits DNA methylation and the activity in myeloid leukemia. Therefore,we investigated combining these two drugs in human leukemia cell line K562. Methods The effects of IM and DAC was examined in K562 cells including cell viability using MTT method,cell cycle phase and cell death using flow cytometric (FCM),and the expression of bcr-abl mRNA by RT-PCR. Results Both DAC and IM resulted in time and concentration-dependent induction of cell death. DAC and IM in combination produced a greater inhibition of growth against K562 cells (F =43.947,165.580,321.193,296.101,P<0.05). The main effect and interaction between two drugs was statistically significant (F = 202.759,168.457,417.538,P <0.001) after 24 h,48 h,72 h and a greater reduction in expression of bcr-abl mRNA than either agent alone. The difference was statistically significant (F =71.981,P <0.05). The number of G1 phase cells were increased significantly when induced by single agent. 48 h incubation with IM 0.2 μmol/L alone or combined with DAC 4 μmol/L showed 6.7 %,8.4 % pre-apoptosis cells,respectively. After incubation for 48 h with DAC 4 μmol/L,the expression of mRNA were decreased by 14 %,IM 0.2 μmol/L showed 40 % reduction,and combination group were significantly depressed for the mRNA expression by 60 %. Conclusion The combination of DAC and IM showed synergistic effects on cell death in K562 cells. These data suggested that DAC used in combination with IM has clinical potential in the treatment of chronic myeloid leukemia.