Hsa-miR-203联合伊马替尼对慢性粒细胞白血病K562细胞的作用

Effect of imatinib combined with hsa-miR-203 gene on chronic myeloid leukemia cell line K562

目的探讨hsa-miR-203联合甲磺酸伊马替尼(mesylate imatinib MI)对人慢性粒细胞白血病K562细胞的影响。方法体外培养K562细胞,利用LipofectamineTM2000将has-miR-203模拟物转染至K562细胞,MTT法检测使用miR-203、MI以及两者联合使用对细胞增殖的抑制率,流式细胞术检测对细胞早期凋亡率的影响。结果 miR-203转染至K562细胞(24、48、72 h)后,联合MI显著抑制K562细胞增殖,抑制效果较各单独使用组作用明显增强。单用miR-203浓度为50μmol·L-1时的抑制率分别为19.69%、25.62%、35.21%。而联合不同浓度(0.5、1、2、3、4μmol·L-1)的伊马替尼,抑制率随着作用时间增加,呈时间—依赖效应。单用hsa-miR-203、伊马替尼及两者联合作用于K562细胞48 h后,早期凋亡率分别为7.8%、8.9%、12.5%。结论当一定浓度的hsa-miR-203与不同浓度的伊马替尼联合之后,对K562细胞的增殖抑制作用增强,hsa-miR-203提高了K562细胞对伊马替尼的敏感性,其机制可能为共同促进K562细胞早期凋亡有关,并为白血病的治疗提供新的依据。

Objective To study the effect of hsa-miR-203 for enhancing the mesylate imatinib sensitivity of leukemic K562 cells. Meth ods We cultured k562 cells in vitro, and hsa-miRo203 minics was transfected to K562 cells using Lipofectamine^TM 2000. The inhibitory effects of miR-203 ,used singly or combining mesylate imatinib on cell proliferation were detected by MTI＇. The percentage of apoptosis cells was determined by flow cytometry. Results The growth inhibition rates were obivously enhanced when mesylate imatinib combined with miR-203. MiR-203 used singly, the inhibition rates were 19.69% ,25.62% ,35.21%. MiR-203 used with imatinib, the inhibitory effects were increased, and showed a dose-dependent effects,when the same concentrations of miR-203 combined with mesylate imatinib. The early apoptic rates were 7.8% ,8.9% ,and 12.5%. Conclusions Combined use of miR-203 and mesylate imatinib could increase the sensitivity of K562 cells to mesylate imatinib,which provides a novel potential approach for treatment of leukemia.