Effect of diethyldithiocarbamate on proliferation,redif f erentiation, and apoptosis of human hepatoma cells  

二乙基二硫代氨基甲酸钠对人肝癌细胞增殖、再分化与凋亡的作用(英文)

作　　者：康九红[1] 魏亚明[2] 郑荣梁[3] 

机构地区：[1]兰州大学生命科学学院,兰州730000 [2]兰州军区总医院血液科,兰州730050 [3]兰州大学国家应用有机化学重点实验室,兰州中国730000

出　　处：《Acta Pharmacologica Sinica》2001年第9期19-26,共8页中国药理学报（英文版）

基　　金：Project surpported by the Doctoral Program of the Ministry of Education of China

摘　　要：AIM: To examine the effects of diethyldithiocarbamate (DDC) on the proliferation, redifferentiation, and apoptosis in human hepatoma cells. METHODS: Cell surface charge, biochemical changes, cell growth in soft agar, single cell electrophoresis, electron microscopy examination, and flow cytometry analysis were measured. RESULTS: After being treated with DDC 3 mmol/L the growth curve and mitotic index of human hepatoma cells decreased remarkably, and the cellular growth inhibitory rate amounted to 52.4 % . The indices related with cell malignancy were alleviated significantly, such as the cell surface charge decreased significantly, the electrophoresis rate dropped from 1.6 to 0.8 μm·s-1·V-1·cm-1, the average value of a-fetoprotein (a-FP) content decreased from 314 to 95μg/g (protein), and r-glutamyl-transpeptidase (γ-GT) activity from 0.9 to 0.14 U/g (protein). The cell differentiation index increased significantly, such as the average levels of tyrosine-a-ketoglutarate transaminase (TAT) activity increased from 11.6 to 36 μmol/g (protein), and the colonogenic potential decreased by 95.6 % . The apoptotic bodies, detached cells, and apoptotic morphological features appeared, and the treated cells’ DNA was fragmented as observed by the comet assay. The flow cytometric results showed that a 42.9 % fractional DNA contentexisted in the treated cells. CONCLUSION: DDC can inhibit human hepatoma cells proliferation, and can induce redifferentiation as well as apoptosis.目的:测定二乙基二硫代氨基甲酸钠(DDC)对人肝癌细胞增殖、再分化与凋亡的作用。方法:采用细胞表面电荷、生化变化、软琼脂细胞生长、单细胞电泳、电子超微结构和流式细胞DNA片断分析等 指标测定细胞分化和凋亡。结果:用DDC 3mmol/L处理后,肝癌细胞的生长和分裂指数显著下降,增殖抑制率达52.4％。与恶化有关的指标显著减轻,如细胞表面电荷明显降低,电泳率从1.6降低到0.8μm·s^(-1)·V^(-1)·cm^(-1),甲胎蛋白由314降为95μg/g(protein),γ-谷氨酰转氨酶活性由0.9降到0.14U/g(protein)。与分化相关的酪氨酸-α-酮戊二酸转氨酶活性显著上升,由11.6升高到36μmol/g(protein),细胞克隆形成力降低95.6％。同时,处理细胞出现了凋亡小体、不贴壁细胞以及其它凋亡特征,且处理细胞DNA发生片断化,流式细胞分析显示处理组42.9％的DNA发生断裂。结论:DDC能够抑制人肝癌细胞增殖,并诱导细胞分化和凋亡。

关 键 词：DIETHYLDITHIOCARBAMATE hepatocellular carcinoma cell division cell differentiadon APOPTOSIS agar gel electrophoresis electron microscopy flow cytometry 

分 类 号：R9[医药卫生—药学]