地西他滨联合去甲氧柔红霉素对DNMT3A突变阳性AML细胞的增殖和凋亡的影响

[目的]探讨地西他滨(DAC)联合去甲氧柔红霉素(IDA)对伴DNA甲基转移酶3A基因(DNMT3A)突变阳性急性髓系白血病(AML)细胞株OCI-AML3的增殖抑制和促凋亡作用.[方法]使用不同浓度IDA单药或联合低浓度DAC(2 μmol/L)干预OCI-AML3细胞48 h后,采用MTT检测细胞增殖,流式细胞术检测细胞凋亡.[结果]相对低浓度的IDA(≤40 nmol/L)对OCI-AML3细胞无显著增殖抑制效应;2 μmol/L DAC联合IDA对OCI-AML3细胞的增殖抑制率显著高于IDA单药(P<0.01);DAC联合IDA能显著提高OCI-AML3细胞的凋亡率(P<0.001).[结论]伴DNMT3A突变的AML细胞对相对低浓度的IDA原发耐药,而DAC可提高其对IDA的敏感性.

Anti-Proliferation and Pro-apoptosis Effects of Decitabine Combined with Idarubicin on AML Cells Harboring Mutant DNMT3A

[Objective]To evaluate the antiproliferation and pro-apoptotic effects of decitabine (DAC) combined with idarubicin (IDA) on OCI-AML3 cells harboring mutant DNMT3A.[Methods]OCI-AML3 cells were treated with different concentrations of IDA singly or combined with 2μM DAC for 48 h.Then,MTT and Annexin-V/PI were used to examine the proliferation and apoptosis of OCI-AML3 cells.[Results]IDA at relatively low concentrations (≤40nM) did not inhibit proliferation of OCI-AML3 cells significantly,but promoted proliferation inhibition remarkably when combined with 2μM DAC (P<0.01).DAC combined with IDA induced higher apoptotic rate compared to DAC or IDA as a single agent (P<0.001).[Conclusion]AML cells harboring mutant DNMT3A are primarily resistant to IDA at relatively low concentrations,while DAC can increase the susceptibility to IDA.