高三尖杉酯碱激活ATM/p53通路抑制人肝癌细胞PLC5增殖  

Homoharringtonine activates ATM/p53 pathway to inhibit proliferation of human liver cancer cell PLC5

作　　者：杜玉梅 唐加峰 黄世莹 张滔 卢睿瑾 何爽 徐航 李静[2] 冉建华[4] 陈地龙[2,3] DU Yu-mei;TANG Jia-feng;HUANG Shi-ying;ZHANG Tao;LU Rui-jing;HE Shuang;XU Hang;LI Jing;RAN Jian-hua;CHEN Di-long(College of Public Health and Management,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China;Lab of Stem Cells and Tissue Engineering,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China;Chongqing Three Gorges Medical College,Chongqing 404120,China;Center of Neuroscience Research,College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学公共卫生与管理学院,重庆400016 [2]重庆医科大学基础医学院干细胞与组织工程研究室,重庆400016 [3]重庆三峡医药高等专科学校,重庆404120 [4]重庆医科大学基础医学院神经科学研究中心,重庆400016

出　　处：《中国药理学通报》2021年第3期380-385,共6页Chinese Pharmacological Bulletin

基　　金：重庆市教委重点项目(No KJZDK201802701)。

摘　　要：目的探讨高三尖杉酯碱(homoharringtonine,HHT)对肝癌细胞PLC5增殖的影响及其可能的机制。方法采用CCK-8以及EdU检测HHT对PLC5细胞增殖的影响;流式细胞术检测HHT对PLC5细胞周期的影响;Western blot检测周期相关蛋白CyclinA、CDK2、p21以及p53、ATM的表达。结果CCK-8结果显示,HHT(0、5、10、20、40、80μg·L^(-1))分别作用PLC5细胞24、48、72 h后,HHT对PLC5细胞的抑制率明显升高,且呈现浓度和时间依赖性;EdU结果显示,经HHT作用后,PLC5细胞增殖能力明显减弱;流式细胞结果显示,HHT可将PLC5细胞阻滞在S期;Western blot结果显示,HHT可上调PLC5细胞中p21、p53以及ATM的蛋白水平,并下调PLC5细胞中CyclinA、CDK2的蛋白水平。结论HHT可诱导PLC5细胞发生DNA损伤,激活DNA损伤修复信号通路,阻滞细胞周期,从而抑制细胞增殖。Aim To explore the effect of homoharringtonine(HHT)on the proliferation of liver cancer cell PLC5 and its possible mechanism.Methods CCK-8 and EdU were used to detect the effect of HHT on the proliferation of PLC5 cells;flow cytometry was employed to assess the effect of HHT on cell cycle of PLC5;Western blot was applied to measure the expression levels of cycle-related proteins cyclinA,CDK2,p21,p53 and ATM.Results Treated with HHT(0,5,10,20,40,80μg·L^(-1))for 24,48,and 72 hours,the inhibitory rates of HHT on PLC5 cells significantly increased in a dose-and time-dependent manner;and PLC5 cell proliferation ability was significantly weakened after HHT treatment;HHT blocked PLC5 cells in S phase;Western blot results revealed that HHT could up-regulate p21,p53 and ATM protein levels in PLC5 cells,and down-regulate cyclinA,CDK2 protein levels in PLC5 cells.Conclusions HHT can induce DNA damage in PLC5 cells,activate the DNA damage repair signal pathway,block the cell cycle,and inhibit cell proliferation.

关 键 词：高三尖杉酯碱 肝细胞癌 PLC5 CDK2 p53 DNA损伤 

分 类 号：R329.4[医药卫生—人体解剖和组织胚胎学] R329.28[医药卫生—基础医学]