α-干扰素增强耐药性白血病K562/ADM细胞及其白血病干细胞对阿霉素的敏感性

Enhancement of sensitivity of multidrug-resistant leukemia K562/ADM cell line and its leukemia stem cells to adriamycin by interferon alpha

目的研究α-干扰素(interferon alpha,IFN-α)对白血病多药耐药K562/ADM群体细胞及其白血病干细胞(LSC)对细胞周期特异性药物阿霉素敏感性的影响。方法以K562/ADM耐药细胞为靶细胞,采用噻唑蓝(MTT)比色法检测细胞增殖活性;流式细胞术碘化丙啶(PI)染色和AnnexinV/PI双染色分别测定细胞周期分布和细胞凋亡;抗CD34、CD38和CD123抗体以及Annexin V共染色检测群体细胞中LSC的含量及凋亡率。结果 IFN-α作用后K562/ADM细胞周期分布发生改变,G0/G1期细胞比例减少,S期细胞比例增高。IFN-α与阿霉素联合作用,明显增强阿霉素对K562/ADM细胞的增殖抑制作用,细胞凋亡率增高。IFN-α可提高K562/ADM细胞群体中LSC的含量(比例),且增加LSC对阿霉素的敏感性,凋亡的LSC数量增高。结论 IFN-α促进K562/ADM群体细胞及其LSC进入细胞增殖周期而提高对细胞周期特异性抗癌药物阿霉素的敏感性。

Aim To investigate the effect of interferon alpha（IFN-α） on the sensitivity of multidrug resistant leukemia K562/ADM cell population and its leukemia stem cells（LSC） to the cell-cycle specific agent adriamycin.Methods The drug-resistant leukemia K562/ADM cells were used as the target cells.The cell proliferating activity was assessed with an MTT colorimetric assay.Flow Cytometry（FCM） was employed to determine the distribution of cell cycle,and the cellular apoptosis was assayed with FITC-Annexin V and propidium iodide（PI） double staining.The proportion and apoptosis of LSC in K562/ADM cell population were determined with co-staining of anti-CD34,anti-C38,anti-CD123 antibodies and Annexin V.Results After the treatment with IFN-α,the K562/ADM cells exhibited obvious changes in the cell cycle distribution,the cells in G0/G1 phase decreased and those in S phase increased.Combination of IFN-α and adriamycin significantly augmented the proliferation-inhibiting and apoptotic effects of adriamycin to K562/ADM cells,and the apoptotic rate of the population cells signally increased.Furthermore,IFN-α could increase the proportion of LSC in K562/ADM cell population and improve the sensitivity of LSC to adriamycin,and the amount of apoptotic LSC（Annexin V＋） significantly increased.Conclusion IFN-α possesses the potential to improve the sensitivity of drug-resistant K562/ADM cell population and its LSC to the cell-cycle specific agent adriamycin by driving the cells to enter the cell division cycle.