注射用核糖核酸Ⅱ通过活性氧介导的PI3K/Akt信号通路诱导人白血病细胞KG1a凋亡  

Ribonucleic acid Ⅱ induces apoptosis of human leukemia KG1a cells through PI3K/Akt activation mediated by reactive oxygen

作　　者：郭珮 李静[1] 冉建华[3] 陈地龙[1,4] 何菲[3] 吕晓婷[1] 石雪萍[1] 李海星[1] GUO Pei;LI Jing;RAN Jian-hua;CHEN Di-long;HE Fei;LYU Xiao-ting;SHI Xue-ping;LI Hai-xing(Lab of Stem Cells and Tissue Engineering,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China;Dept of Pharmacy,Occupational Disease Prevention Hospital,Chongqing 400060,China;Dept of Anatomy,College of Basic Medicines,Chongqing Medical University,Chongqing 400016,China;Chongqing Three Gorges Medical College,Chongqing 404120,China)

机构地区：[1]重庆医科大学基础医学院组织细胞工程与干细胞研究室,重庆400016 [2]重庆市第六人民医院/重庆市职业病防治院药学部,重庆400060 [3]重庆医科大学基础医学院解剖学教研室,重庆400016 [4]重庆三峡医药高等专科学校,重庆404120

出　　处：《中国药理学通报》2019年第8期1092-1098,共7页Chinese Pharmacological Bulletin

基　　金：重庆市科技计划项目(No cstc2015jcyjA0036)

摘　　要：目的 研究注射用核糖核酸Ⅱ诱导人急性骨髓白血病细胞系KG1a细胞凋亡与PI3K/Akt信号通路和活性氧(ROS)的关系。方法 流式细胞术(FCM)检测细胞周期和细胞内的ROS水平;免疫印迹法(Western blot)检测PI3K/Akt信号通路相关蛋白p-PI3K、p-Akt、p-MDM2、p21和周期相关蛋白cyclin D1、CDK4的表达;加入抗氧化剂N-乙酰半胱氨酸(NAC)后,检测p-PI3K、p-Akt和p53蛋白表达变化。结果 FCM结果显示,注射用核糖核酸Ⅱ可将KG1a细胞阻滞在G 0/G 1期,且ROS介导了细胞周期的阻滞;FCM检测ROS结果显示,KG1a细胞内ROS水平均随药物浓度增加而升高;Western blot结果显示,注射用核糖核酸Ⅱ下调p-PI3K、p-Akt、p-MDM2和cyclin D1、CDK4的表达,上调p21的表达;与仅用注射用核糖核酸Ⅱ相比,经NAC预处理后再使用注射用核糖核酸Ⅱ,明显上调了磷酸化PI3K和Akt的表达,下调了p53的表达。结论 注射用核糖核酸Ⅱ通过ROS介导的PI3K/Akt信号通路,诱导人急性骨髓白血病细胞系KG1a细胞凋亡。Aim To investigate the correlation between ribonucleic acid Ⅱ on human leukemia cell lines KG1a and PI3K/Akt signaling pathway by reactive oxygen.Methods The cell cycle and the ROS level of ribonucleic acid Ⅱ in human leukemia cell lines were determined by flow cytometry.The levels of p-PI3K,p-Akt,p-MDM2,p21,cyclin D1 and CDK4 were detected by Western blot.The expression levels of protein p-PI3K,p-Akt and p53 after treated with ribonucleic acid Ⅱ and NAC were also detected by Western blot.Results The results of FCM revealed that the cell cycle was arrested at G 0/G 1 phase and ROS prevented the arrest of cell cycle.The results also showed that ROS level increased with the concentration of ribonucleic acid Ⅱ in KG1a cells.Western blot results showed after treated with ribonucleic acid Ⅱ,the expression levels of p-PI3K,p-Akt,p-MDM2,cyclin D1 and CDK4 decreased,while p21 increased in KG1a cells.After treated with ribonucleic acid Ⅱ and NAC,the expression levels of p-PI3K and p-Akt increased,while p53 decreased.Conclusion Ribonucleic acid Ⅱ can induce the apoptosis of leukemia KG1a cells through ROS-mediated PI3K/Akt signaling pathway.

关 键 词：注射用核糖核酸Ⅱ 白血病 KG1a PI3K/AKT 活性氧 凋亡 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R329.28[医药卫生—基础医学]