虫草素对肝癌HepG2细胞增殖和凋亡的影响  

Effects of cordycepin on the proliferation and apoptosis of hepatocellular carcinoma HepG2 cells

作　　者：刘佳[1,2] 李亚萍 王泽昊 王宣军 盛军[1] LIU Jia;LI Ya-ping;WANG Ze-hao;WANG Xuan-jun;SHENG Jun(Key Laboratory of Pu-er Tea Science,Ministry of Education,Yunnan Agricultural University,Kunming 650201,Yunnan Province,China;College of Science,Yunnan Agricultural University,Kunming 650201,Yunnan Province,China;College of Food Science and Technology,Yunnan Agricultural University,Kunming 650201,Yunnan Province,China)

机构地区：[1]云南农业大学普洱茶学教育部重点实验室,云南昆明650201 [2]云南农业大学理学院,云南昆明650201 [3]云南农业大学食品科学技术学院,云南昆明650201

出　　处：《中国临床药理学杂志》2021年第14期1794-1797,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨虫草素对HepG2细胞增殖和凋亡的影响。方法用0(对照组),100,200,400,600,800和1000μmol·L^(-1)虫草素处理HepG2细胞24 h和48 h后,用噻唑蓝法检测细胞存活率。将HepG2细胞分为对照组和低、高剂量实验组,并分别用0,200和400μmol·L^(-1)虫草素处理48 h。用克隆形成实验检测细胞恶性程度,用Annexin V-FITC/PI检测细胞凋亡水平,用RNA-seq鉴定虫草素引起哪些信号通路的改变。结果虫草素呈剂量和时间依赖性地抑制HepG2细胞增殖。干预48 h后,低、高剂量实验组和对照组的细胞凋亡率分别为(7.56±0.91)%,(13.70±1.77)%和(4.77±0.52)%,细胞克隆形成能力分别为0.31±0.04,0.17±0.03和1.05±0.12,低、高剂量实验组的上述指标和对照组比较,差异均有统计学意义(P<0.05,P<0.01,P<0.001)。RNA-seq结果发现:在虫草素处理后,转录因子复合物激活蛋白1(AP1信号通路)的信号显著下调,内质网未折叠蛋白反应的信号显著上调。结论虫草素可以显著地抑制肝癌细胞的生长和恶性转化,而这个过程很可能是通过AP1信号通路和内质网未折叠蛋白反应参与调控的。Objective To explore the effect of cordycepin on the proliferation and apoptosis of HepG2 cells.Methods HepG2 cells were treated with 0(control group),100,200,400,600,800 and 1000μmol·L^(-1)cordycepin for 24 h and 48 h,after that the cell survival rate was detected by methyl thiazolyl tetrazolium.HepG2 cells were divided into control,experimental-L and experimental-H groups,and treated with 0,200 and 400μmol·L-1 cordycepin for 48 h,respectively.Clonal formation experiments were used to detect the degree of cell malignancy.Annexin V-FITC/PI was used to detect the level of apoptosis.RNA-seq was used to identify the signal pathway changes caused by cordycepin.Results Cordycepin inhibited HepG2 cell proliferation in a dose-and time-dependence manner.After 48 h of intervention,the apoptosis rates in the control,experimental-L and experimental-H groups were(4.77±0.52)%,(7.56±0.91)%and(13.70±1.77)%,the cloning forming abilities were 1.05±0.12,0.31±0.04 and 0.17±0.03.Compared with the control group,the above indexes of the experimental-L and experimental-H groups were significantly different(P<0.05,P<0.01,P<0.001).The results of RNA-seq showed that after cordycepin treatment,the signal of transcription factor complex activating protein 1(AP1 signal pathway)was significantly down-regulated and the signal of endoplasmic reticulum unfolded protein response was significantly up-regulated.Conclusion Cordycepin can inhibit the growth and malignant transformation of hepatoma cells probably by regulating the AP1 signaling pathway and endoplasmic reticulum unfolded protein reaction.

关 键 词：虫草素 HepG2细胞 转录因子复合物激活蛋白1 内质网未折叠蛋白反应 

分 类 号：R28[医药卫生—中药学]