【摘要】 用 1mg·L-1 三尖杉酯碱 (Harringtoning ,HT)处理人早幼粒急性白血病HL 6 0细胞2h ,诱导细胞出现明显的凋亡 (Apoptosis ,Apo)形态学和生化特征 ,包括染色质凝集、Caspase 3(天冬氨酸特异的半胱氨酸蛋白水解酶 3)活化、DNA断裂等 .来自HL 6 0的多药抗性细胞HR2 0和HT9抗HT诱导的凋亡 ,一般认为是P 糖蛋白 (P GP 170 )对药物的外排作用引起细胞对凋亡的抗性 .但用 2mg·L-1 CsA(CysclosporineA)逆转抗性细胞对药物的外排作用 ,1mg·L-1 HT作用 4 8h仍不能诱导HR2 0和HT9细胞凋亡 ,说明HR2 0和HT9多药抗性细胞抗HT诱导凋亡的机制不仅仅在于细胞膜上的P 糖蛋白对药物的外排作用 ,可能还有凋亡相关因子或其他因素参与作用 .Caspase 3是细胞凋亡通路中的一个中心环节 ,HR2 0和HT9抗HT诱导的Caspase 3活化 ,这可能是HR2 0和HT9不能凋亡的一个重要原因 .更多还原

【Abstract】 When treated with 1 mg·L -1 Harringtoning(HT) for 2 h, the HL-60 cells show obvious apoptotic character, such as chromatin concentration, Caspase-3 and activation and DNA fragmentation etc. Multidug-resistant cells HR20 and HT9 derived from HL-60 cell resist HT induced apoptosis. Exffluxion of drug by P-glycoprotein used to be thought of an important reason of apoptosis resistant. But when the drug exffluxion function of P-glycoprotein is reversed by CsA, HT still cannot induce apoptosis in the multidrug-resistant cells. This shows that the anti-apoptotic mechanism of HR20 and HT9 cells relates to not only the P-glycoprotein, but also some other factors related to apoptotis. HR20 and HT9 cells also resist Caspase-3 activation and DFF45 degradation. Caspase-3 activation is a key matter of most apoptotic pathway. HR20 and HT9 resist Caspase-3 activation induced by HT, it may be an important reason for apoptotic-resistance.更多还原