芹菜素激活TRAIL死亡受体参与诱导胃癌SGC-7901细胞凋亡的实验研究  

Activation of the TRAIL death receptor by apigenin for induction of apoptosis in the gastric cancer SGC-7901 cells

作　　者：崔昭阳 李素娜 姜旭倩 王弈丹 侯丽颖 CUI Zhaoyang;LI Suna;JIANG Xuqian;WANG Yidan;HOU Liying(School of Public Health,North China University of Science and Technology,Tangshan 063210;School of Science,North China University of Science and Technology,Tangshan 063210,Hebei,China)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063210 [2]华北理工大学理学院,河北唐山063210

出　　处：《癌变．畸变．突变》2021年第1期32-36,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：河北省自然科学基金(H2019209453);华北理工大学博士启动基金(BS2017058)。

摘　　要：目的:研究芹菜素(API)对人胃癌SGC-7901细胞的增殖抑制和凋亡诱导作用,并探讨API诱导胃癌细胞凋亡的机制。方法:设置对照组及不同浓度(20、40、60、80μmol/L)的API组,分别作用SGC-7901细胞12、24和48 h后,CCK-8法检测细胞增殖率。选择作用24 h为后续处理时间点,采用流式细胞术检测细胞凋亡率;Western blot检测TRAIL通路中死亡受体DR4、DR5蛋白的表达水平;采用RNAi技术,用DR4 siRNA和DR5 siRNA分别沉默TRAIL通路中死亡受体DR4和DR5表达,设置对照组、API组、DR4 siRNA+API组、DR5 siRNA+API组,作用细胞24 h后,流式细胞术检测各组细胞凋亡率。结果:细胞增殖检测结果提示API对人胃癌SGC-7901细胞的增殖率具有明显抑制作用,呈现浓度依赖性(r12 h=-0.99,r24 h=-0.88,r48 h=-0.89,均为P<0.05);流式细胞术检测结果提示细胞凋亡率随着API作用浓度的增加而升高(r=0.96,P<0.05);Western blot检测发现API作用可上调细胞中DR4、DR5蛋白的表达水平;DR4 siRNA和DR5 siRNA分别沉默DR4和DR5的表达后,与API组相比,DR4 siRNA+API组和DR5 siRNA+API组的细胞凋亡率均降低(P<0.05)。结论:芹菜素具有抑制人胃癌SGC-7901细胞增殖和诱导细胞凋亡的作用,其机制可能与TRAIL通路中死亡受体DR4、DR5蛋白的表达被激活有关。OBJECTIVE:To investigate effects of apigenin(API)on proliferation and apoptosis induction in the human gastric cancer SGC-7901 cells.METHODS:SGC-7901 cell cultures were organized into different groups:control and API-treated groups.The latter groups were treated with 20,40,60 and 80μmol/L API for 12,24 and 48 h.Cell proliferation rates were detected using the CCK-8 method,apoptosis rates by flow cytometry,and expression levels of death receptors DR4 and DR5 proteins in the TRAIL pathway by Western blot.Using RNAi technology,DR4 siRNA and DR5 siRNA were used to silence the expression of death receptors DR4 and DR5,respectively.Apoptosis rates after 24 h treatments for the control,API,DR4 siRNA+API and DR5 siRNA+API groups were determined using flow cytometry.RESULTS:The results indicated that API significantly inhibited proliferation rates of SGC-7901 cells in a concentration-dependent way(r12 h=-0.99,r24 h=-0.88,r48 h=-0.89,all P<0.05).Apoptosis rates increased with increased API concentrations(r=0.96,P<0.05).In addition,API treatment up-regulated the expression levels of DR4 and DR5 proteins.When the expressions of DR4 and DR5 were silenced by their respectively siRNAs,the apoptosis rates for the DR4 siRNA+API and the DR5 siRNA+API groups were reduced compared with the API group(P<0.05).CONCLUSION:Our results indicated that apigenin inhibited the proliferation rates and induced apoptosis in the human gastric cancer SGC-7901 cells.The observed changes might be mediated by apigenin-activation of the death receptors DR4 and DR5 proteins in the TRAIL pathway.

关 键 词：芹菜素 胃癌 肿瘤坏死因子相关凋亡诱导配体 死亡受体 凋亡 

分 类 号：R730.2[医药卫生—肿瘤]