Embelin通过氧化应激途径导致DNA损伤抑制HL-60细胞增殖  

Involvement of oxidative stress in embelin-induced cell death in leukemia HL-60 cells

作　　者：杨莹[1] 胡荣[1] 朱珂[1] 李迎春[1] 李佳[1] 苗苗[1] 王洪涛[1] 姚鲲[1] 刘卓刚[1] 

机构地区：[1]中国医科大学附属盛京医院,沈阳110005

出　　处：《中华血液学杂志》2015年第6期465-468,共4页Chinese Journal of Hematology

摘　　要：目的 探讨Embelin是否通过氧化应激途径导致DNA双链损伤,从而抑制HL-60细胞增殖.方法 HL-60细胞经不同浓度（3、10、30、100及300 μg/ml）Embelin处理24 h,采用CCK-8法检测细胞增殖抑制率;采用DCFH-DA荧光探针流式细胞术测定细胞内活性氧（ROS）水平;彗星试验检测DNA双链断裂（DSB）情况.结果 与对照组相比,Embelin浓度为10、30、100及300 μg/ml时均可显著抑制HL-60细胞增殖,增殖抑制率分别为（12.74±2.27）％、（23.49±1.96）％、（30.30±1.89）％和（57.55±3.59）％（P值均＜0.05）;随着药物浓度的增加HL-60细胞内ROS的水平增高、DSB增加（p值均＜0.05）;应用ROS抑制剂N-乙酰-L-半胱氨酸（NAC）预先处理HL-60细胞2h后再加入300 μg/ml的Embelin作用24 h,与单用300 μg/ml Embelin作用组比较,ROS水平下降、DSB减少,同时Embelin对HL-60细胞的抑制率由（57.55±3.59）％下降为（32.75±2.70）％（P值均＜0.05）.结论 Embelin通过产生细胞内ROS发生氧化应激作用,导致DSB,最终抑制HL-60细胞的增殖.Objective To evaluate the effects of Embelin on HL-60 cells by the impact of oxidative stress on DNA double-strain breaks（DSBs）.Methods HL-60 cells were treated with Embelin in different concentration（3,10,30,100,and 300 tg/ml） for 24 h,and inhibitory effects was examined by CCK-8 assay.Reactive oxygen species （ROS） levels were evaluated by flow cytometry using DCFH-DA.Comet assay was used to detect the extent of DSBs.Results Embelin inhibited proliferation of HL-60 cells in a dose-dependent manner.At the concentration of 10,30,100,and 300 μg/ml,the inhibition rate was （12.74±2.27）％,（23.49±1.96）％,（30.30±1.89）％,and （57.55± 3.59）％ （P＜0.05）.Embelin also lead to high level of intracellular ROS and deterioration of DNA damage （P＜0.05）.When HL-60 cells were pretreated with ROS scavenger N-acetyl-l-cysteine（NAC） for 2 h and then treated with 300 μg/ml Embelin for 24 h,the intracellular ROS level declined and DSBs relieved （P＜0.05）.Meanwhile,embelin-induced cell viability significantly declined to（32.75±2.70）％（P＜0.05）.Conclusions Embelin induced the death of HL-60 cells by increasing the generation of intracellular oxidation and the oxidative stress,which drived the damage of DNA double-strand.

关 键 词：酸藤子属 白血病 活性氧 氧化性应激 DNA双链断裂 

分 类 号：R733.7[医药卫生—肿瘤]