木香烃内酯对肝癌SMMC-7721细胞凋亡的影响及其作用机制  

Effect of costunolide on apoptosis of hepatocellular carcinoma SMMC-7721 cells and relevant mechanism

作　　者：刘丹[1] 张永慧[1] 何秀贞[1] 熊书[1] 马羚[1] 冯彬彬[1] 冯晓灵[1] LIU Dan;ZHANG Yong-hui;HE Xiu-zhen;XIONG Shu;MA Ling;FENG Bin-bin;FENG Xiao-ling(Chongqing Three Gorges Medical College,Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area,Chongqing 404020,China)

机构地区：[1]重庆三峡医药高等专科学校三峡库区道地药材开发利用重庆市重点实验室,重庆404020

出　　处：《中国生物制品学杂志》2022年第10期1195-1199,共5页Chinese Journal of Biologicals

基　　金：重庆市教委科学技术研究项目(KJQN201902710);重庆市教委科学技术研究项目(KJ-1602502);重庆市科学技术局自然科学基金(基础研究与前沿探索专项)面上项目(cstc2019jcyj-msxm X0607);重庆市卫计委重庆市科技局中医药科研项目(ZY201802054);重庆三峡医药高等专科学校重点项目(2016xzz02);重庆三峡医药高等专科学校重点项目(2016xzz05)。

摘　　要：目的 探讨木香烃内酯(costunolide,Cos)对肝癌SMMC-7721细胞凋亡的影响及其作用机制。方法 将SMMC-7721细胞随机分为对照组、10、20、30μmol/L Cos剂量组。采用流式细胞术检测Cos对SMMC-7721细胞凋亡的影响,Western blot检测SMMC-7721细胞中凋亡相关蛋白(Bax、Bcl-2、Caspase-3)及内质网应激(endoplasmic reticulum stress,ERS)通路相关蛋白(GRP78、CHOP、ATF4)的表达水平。结果 10、20和30μmol/L Cos剂量组SMMC-7721细胞凋亡率(apoptosis rate,AR)均明显高于对照组(P <0.05),且各Cos剂量组SMMC-7721细胞AR随剂量增加明显上升(P <0.01)。与对照组比较,20和30μmol/L Cos剂量组SMMC-7721细胞中Bcl-2蛋白表达水平明显降低(P <0.05),Bax蛋白表达水平均明显增加(P <0.05),10μmol/L Cos剂量组的Bcl-2及Bax蛋白表达水平差异无统计学意义(P> 0.05);各组SMMC-7721细胞中Caspase-3蛋白表达水平差异无统计学意义(P> 0.05);10、20μmol/L Cos剂量组SMMC-7721细胞中GRP78、CHOP、ATF4蛋白表达水平均明显升高(P <0.05)。结论 Cos可通过激活ERS通路促进诱导肝癌SMMC-7721细胞凋亡。Objective To investigate the effect of costunolide(Cos)on apoptosis of hepatocellular carcinoma SMMC-7721cells and the relevant mechanism. Methods SMMC-7721 cells were randomly divided into one control and three test groups. The cells in control group were untreated,while those in three test groups were treated with 10,20 and 30 μmol/L Cos respectively. The effect of Cos on apoptosis of SMMC-7721 cells were evaluated by flow cytometry,while the expression levels of apoptosis-related proteins(Bax,Bcl-2 and Caspase-3)and endoplasmic reticulum stress(ERS)pathwayrelated proteins(GRP78,CHOP and ATF4) were determined by Western blot. Results The apoptosis rates(ARs) of SMMC-7721 cells in three test groups were significantly higher than that in control group(P < 0. 05) and increased significantly with the increasing Cos dose(P < 0. 01). Compared with those in control group,the expression levels of Bcl-2protein in SMMC-7721 cells treated with 20 and 30 μmol/L Cos decreased significantly(P < 0. 05),while those of Bax protein increased significantly(P < 0. 05),and those of Bcl-2 and Bax proteins in the cells treated with 10 μmol/L Cos showed no significant difference(P > 0. 05). However,there was no significant difference in the expression level of Caspase-3 protein in SMMC-7721 cells in various groups(P > 0. 05),and the expression levels of GRP78,CHOP and ATF4 proteins in the cells treated with 10 and 20 μmol/L Cos increased significantly(P < 0. 05). Conclusion Cos promoted the apoptosis of hepatocellular carcinoma SMMC-7721 cells by activating ERS pathway.

关 键 词：木香烃内酯 肝癌 SMMC-7721细胞 细胞凋亡 内质网应激 

分 类 号：R285.5[医药卫生—中药学]