摘要
目的 :探讨青蒿琥酯 (artesunate ,Art)诱导人急性早幼粒白血病细胞HL6 0凋亡的线粒体机制。方法 :用Art处理HL6 0细胞 ,通过MTT比色法检测细胞增殖抑制的效果 ;透射电镜、DNA凝胶电泳技术观察细胞的凋亡 ;流式细胞术 (flowcytometry ,FCM)进行细胞周期分析和线粒体膜电位 (mitochon drialmembranepotential ,MMP)水平的检测 ;比色法检测半胱 天冬氨酸蛋白酶 3(cysteinecontainingas partate,Caspase 3)活性。结果 :Art呈浓度和时间依赖性的抑制HL6 0细胞的增殖 (P <0 .0 5 )。Art诱导后HL6 0细胞出现典型的凋亡形态学变化和生化改变 ,G2 +M期细胞比例增高 ,S期减少 ,凋亡率上升 (P <0 .0 5 ) ,线粒体膜电位降低 (P <0 .0 5 ) ,Caspase 3活性增强 (P <0 .0 5 )。结论 :Art可能通过线粒体 半胱 天冬氨酸蛋白酶 3特定途径诱导HL6 0细胞凋亡。
AIM: To explore mitochondrial mechanisms of apoptosis induced by artesunate in human leukemia HL60 cells. METHODS: Human leukemia HL60 cell lines were treated by artesunate. The inhibitory effect on cell proliferation was assessed by MTT assay. Electron microscopy and DNA gel electrophoresis was applied to demonstrate the presence of apoptosis. The level of MMP, cell cycle were determined by flow cytometry (FCM). The activity of caspase 3 was observed by colorimetry. RESULTS: Art showed a dose dependent and time dependent manner on the growth of HL60 cells (P< 0.05 ). The typical apoptotic morphological and biochemical changes showed in apoptosis of HL60 cells induced by Art. The flow cytometric profiles revealed that Art(200 mg·L -1 ) led to the shift from 7.3 % up to 18.2% of the G 2+ M phase and from 55.3 % down to 16.0 % of the S phase cells in the percentage of HL60 cell with the increased rate of cell apoptosis(P< 0.05 ). Art significantly decreased the level of MMP in HL60 (P< 0.05 ), and enhanced the activity of caspase 3 (P< 0.05 ). CONCLUSION: Art can induce apoptosis in HL60 via a mitochondria/caspase3 specific pathway.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2005年第2期176-179,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
