二乙酰二脱水卫矛醇诱导白血病HL-60细胞凋亡及其机理(英文)  

APOPTOSIS INDUCED BY DIACETYLDIANHYDROGALACTITOL AND ITS MECHANISM IN HL-60 LEUKEMIA CELLS

作　　者：杨锦南[1] 刘巨源[1] 许华[2] 刘晓丽[1] 秦豫[1] 

机构地区：[1]新乡医学院药理学教研室,河南新乡453003 [2]暨南大学药理学教研室,广东广州510632

出　　处：《药学学报》2002年第9期691-695,共5页Acta Pharmaceutica Sinica

摘　　要：目的　研究二乙酰二脱水卫矛醇 (DADAG)诱导人白血病HL 60细胞凋亡及其机理。方法　MTT法观察DADAG的体外抗增殖作用 ;透射电镜、DNA梯形条带和流式细胞仪检测HL 60细胞凋亡 ;Westernblotting法和caspase 3检测试剂盒分析DADAG诱导HL 60细胞凋亡与Bcl 2家族成员和caspase 3的关系。结果　DADAG明显抑制HL 60细胞增殖和诱导细胞发生凋亡。 8μg·mL- 1 DADAG处理HL 60细胞不同时间后 ,Bcl XL 蛋白水平呈时间依赖性地下降 ,而Bad蛋白水平上调。DADAG处理HL 60细胞 2 4h后 ,caspase 3酶活性达峰值。Caspase 3抑制剂z DEVD .fmk可部分逆转DADAG诱导HL 60细胞凋亡的作用 ,而caspases广谱抑制剂z VAD .fmk可完全逆转此作用。结论　DADAG诱导HL 60细胞凋亡依赖caspase 3途径的激活 ,而caspase 3的激活可能与BclAIM To investigate the apoptosis induced by diacetyldianhydrogalactitol (DADAG) and its mechanism in human HL 60 leukemia cells. METHODS Inhibition of proliferation was measured by MTT assay. DADAG induced apoptosis in HL 60 cells was observed by electron microscopy, flow cytometry and DNA frag mentation assay. The levels of Bcl 2 family proteins were detected by Western b lotting. Caspase 3 activity was determined by ApoAlert CPP32 colorimetric assay kit. RESULTS DADAG exhibited potent antiproliferative activity and induced apoptosis in HL 6 0 cellls. After treatment with DADAG 8 μg·mL -1 for various times, th e Bcl X L protein level decreased in a time dependent manner, while the Bad p rotein level was up regulated. The caspase 3 activity increased markedly after treatment with DADAG for 24 h. The apoptotic signals were suppressed by z VAD. fmk (a general inhibitor of caspases), whereas z DEVD.fmk, a selective inhibito r of caspase 3, only induced partial reversion of the apoptotic effects. CONCLUSION DADAG induced apoptosis in HL 60 cells required caspase 3 activation and casp ase 3 activation was related with Bcl 2 family members.

关 键 词：白血病 二乙酰二脱水卫矛醇 细胞凋亡 HL-60细胞 药理学 

分 类 号：R733.7[医药卫生—肿瘤] R965[医药卫生—临床医学]