【摘要】 目的研究三氧化二砷(arsenic trioxide,ATO)对蛋白酪氨酸激酶抑制剂甲磺酸伊马替尼(imatinib mesy-late,IM)K562/MDR1耐药的逆转作用。方法应用四甲基偶氮唑蓝(MTT)比色法分别检测IM对K562和K562/MDR1细胞的药敏性,计算半数抑制浓度(IC50)及IM对K562/MDR1的耐药倍数;检测ATO对K562/MDR1细胞的药敏性,计算IC50;将非细胞毒作用浓度的ATO与IM联合应用于K562/MDR1,计算此时IM的IC50以及ATO应用后的逆转倍数。应用流式细胞术比较IM单用以及与非细胞毒作用浓度的ATO联合应用后,对K562/MDR1凋亡率的影响,分析ATO对IM敏感性的影响。结果IM存在对K562/MDR1耐药的现象,与亲本K562细胞比较,其耐药倍数为2.51,采用非细胞毒作用的ATO对IM的逆转倍数为1.86,并可提高IM对K562/MDR1的凋亡率。结论IM存在对K562/MDR1的耐药现象,ATO可有效逆转IM耐药,并可增强IM对K562/MDR1细胞的诱导凋亡作用。更多还原

【Abstract】 Objective To investigate the reversal effect of arsenic trioxide(ATO) on the resistance of tyrosine kinase inhibitor imatinib mesylate(IM) to K562/MDR1.Method Methyl-thiazol tetrazolium(MTT) assay is employed to examine the pharmacological effect of IM on K562 and K562/MDR1,to calculate the inhibitor concentration 50(IC50) of IM in these two cell lines and the resistance multiple of IM to K562/MDR1.Examine the pharmacology effect of ATO to K562/MDR1,to calculate its IC50 in this cell line.IM and ATO at a concentration without cytotoxicity were used in K562/MDR1 to calculate the IC50 and the reversal multiple of IM.FCM was employed to compare the effect of IM and ATO at a concentration without cytotoxicity on the inducing apoptosis of K562/MDR1,so as to analyze the pharmacology effect of IM on ATO. Result Phenomen on IM resistance in K562/MDR1 was available,compared with its wild type cell line K562,the resistance multiple was 2.51.ATO at a concentration without cytotoxinic effect was able to reverse the resistance of IM,and the reversal multiple was 1.86,it also was able to enhance the inducing apoptosis effect of IM.Conclusion There is resistance phenomena of IM to K562/MDR1,and ATO is able to reverse the resistance of IM and enhance the inducing apoptosis effect of IM.更多还原