双氢青蒿素对三氧化二砷在肺腺癌细胞的敏感性研究  

Research on the sensibility of dihydroartemisinin on arsenic trioxide in lung adenocarcinoma cell

作　　者：陈虹宇[1] 谷仕艳[1] 张遵真[1] 

机构地区：[1]四川大学华西公共卫生学院(华西第四医院),四川成都610041

出　　处：《现代预防医学》2017年第14期2600-2604,共5页Modern Preventive Medicine

基　　金：国家自然科学基金面上项目(NO.81372945)

摘　　要：目的探讨双氢青蒿素(DHA)是否能增加肺腺癌A549细胞对三氧化二砷(ATO)的敏感性及可能的机制。方法以人肺腺癌A549细胞为研究对象,按处理方式分为对照组、单独DHA或ATO处理组及二者联合组,采用MTT比色法检测DHA和ATO对细胞增殖的影响,彗星实验检测DNA损伤情况,荧光探针检测细胞内活性氧(ROS)水平,流式细胞术检测细胞周期和细胞凋亡。结果与ATO单独处理相比,DHA和ATO联合处理可以显著降低A549细胞存活率,同时显著增加细胞尾部DNA百分率和Olive尾距(OTM)、ROS水平和凋亡率(P<0.05);另外,2种处理方式均可以阻滞细胞于G2/M期,但差异无统计学意义(P>0.05)。结论 DHA可以增强ATO杀死肺腺癌A549细胞的敏感性,其机制可能是DHA和ATO联合处理诱导了细胞内ROS的产生与蓄积,ROS可以引起DNA链断裂,进而阻滞细胞周期进行修复,修复失败的细胞最终走向凋亡。Objective The study aimed to discuss whether dihydroartemisinin （DHA） could increase the sensibility and possible mechanism to arsenic trioxide （ATO） by the cell A549 in adenocarcinoma of lung. Methods Cell A549 in adenoearcinoma of human lung was selected as the research object, the control group, individual DHA or ATO processing group, and combination group of both were divided according to the processing mode. The MTY colorimetric method was adopted to test the impact to cell proliferation by DHA and ATO. The comet assay was applied to test DNA damage condition. The fluorescence probe was used for testing reactive oxygen species （ROS） level. The flow cytometry was introduced for testing cell cycle and cell apoptosis. Results Compared to ATO individual processing, the combination processing between DHA and ATO could reduce the survival rate of cell A549 significantly, and meanwhile could increase DNA percentage at the cell tail, Olive tail moment （OTM）, ROS level and apoptosis rate remarkably （P〈0.05）. In addition, both of the two processing modes could retard cell at G2/M period. However, there is no statistical significance in the difference （P〉0.05）. Conclusion DHA could enhance the sensibility that ATO kills the cell A549 in adenocarcinoma of lung, it could be the combined processing by DHA and ATO had induced ROS generation and accumulation in the cell, ROS could cause DNA chain breaking, and thus to retard repairing cell cycle, repair the failing cell and finally move towards apoptosis.

关 键 词：双氢青蒿素 三氧化二砷 凋亡 敏感性 

分 类 号：R319[医药卫生—基础医学]