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目的 研究三氧化二砷 (As2 O3 )对人多药耐药白血病细胞K5 6 2 ADM的诱导凋亡作用和对P 糖蛋白 (P gp)表达及功能的影响 ,以及As2 O3 与常规化疗药物对耐药细胞的联合效应。方法 以白血病多药耐药细胞系K5 6 2 ADM为As2 O3 作用的靶细胞 ,用MTT比色法检测细胞增殖活性 ,光镜、激光共聚焦显微镜和电镜观察形态学变化 ,流式细胞术进行细胞周期分析和P gp表达的检测 ,激光共聚焦显微镜检测P gp功能。结果 K5 6 2 ADM细胞对阿霉素 (ADM)高度耐受 ,并与柔红霉素 (DNR)和足叶乙甙 (Vp16 )交叉耐药。 0 .5～ 2 0 .0 μmol LAs2 O3 抑制K5 6 2 ADM细胞增殖 ,抑制活性高于K5 6 2细胞。经As2 O3 诱导后K5 6 2 ADM细胞出现典型的凋亡形态学变化和亚G1 期细胞比例增高等凋亡特征性改变。As2 O3 下调K5 6 2 ADM细胞P gp的表达并抑制其功能 ,增加K5 6 2 ADM细胞对ADM、DNR和Vp16的敏感性。结论 As2 O3 能够诱导白血病多药耐药细胞凋亡 ,并通过抑制耐药细胞P gp的表达和功能提高耐药白血病细胞对常规化疗药物的敏感性。
Objective To investigate the effects of arsenic trioxide (As2 O3) on the apoptosis of human multidrug-resistant leukemia K562 ADM cells and its effect on the expression and function of P-glycoprotein (P gp), as well as the effects of As2 O3 and conventional chemotherapeutic drugs on drug- The joint effect. Methods The leukemia multidrug-resistant cell line K5 6 2 ADM was used as a target cell for As 2 O 3. MTT assay was used to detect the cell proliferative activity. Morphological changes were observed under light microscope, confocal laser scanning microscopy and electron microscopy. Flow cytometry Cell cycle analysis and P gp expression were detected by laser confocal microscopy P gp function. Results K5 6 2 ADM cells were highly resistant to doxorubicin (ADM) and were cross-resistant to daunorubicin (DNR) and etoposide (Vp16). 0.5 ~ 2.0 μmol LAs2 O3 inhibited the proliferation of K5 6 2 ADM cells, and the inhibitory activity was higher than that of K5 6 2 cells. After As2 O3-induced K562 ADM cells typical apoptotic morphological changes and sub-G1 phase cells increased apoptosis characteristics such as changes. As2 O3 down-regulated the expression of P gp and inhibited its function in K5 6 2 ADM cells, and increased the sensitivity of K5 6 2 ADM cells to ADM, DNR and Vp16. Conclusion As2 O3 can induce apoptosis of multidrug-resistant cells in leukemia, and improve the sensitivity of multidrug-resistant leukemic cells to conventional chemotherapeutic drugs by inhibiting the expression and function of P gp in drug-resistant cells.