姜黄素对人肝癌SMMC-7721细胞裸鼠移植瘤的抑制作用及其机制  

Inhibitory effect of curcumin on human carcinoma SMMC-7721 cells xenografted in nude mice and its mechanism

作　　者：孙俊[1,2] 徐伟 陆荣柱 朱孝仁[2] 徐新明[1] 蒋一全 陈健[1,2] SUN Jun;XU Wei;LU Rongzhu;ZHU Xiaoren;XU Xinming;JIANG Yiquan;CHEN Jian(Department of Hepatobiliary Surgery, Kunshan Hospital Affiliated to Jiangsu University, Suzhou Jiangsu 215300;School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013;Department of Pathology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yancheng Jiangsu 224001;Center for Experimental Research, Kunshan Hospital Affiliated to Jiangsu University, Suzhou Jiangsu 215300, China)

机构地区：[1]江苏大学附属昆山医院肝胆外科,江苏苏州215300 [2]江苏大学医学院,江苏镇江212013 [3]南京中医药大学附属盐城市中医院病理科,江苏盐城224001 [4]江苏大学附属昆山医院中心实验室,江苏苏州215300

出　　处：《江苏大学学报（医学版）》2022年第3期219-225,230,共8页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金资助项目(81273124);昆山社会科技专项(KS1955)。

摘　　要：目的:探究姜黄素对人肝癌SMMC-7721细胞裸鼠移植瘤的生长抑制作用及其潜在机制。方法:采用人肝癌SMMC-7721细胞建立肝癌移植瘤模型,将20只荷瘤裸鼠均分为对照组和10、50、100 mg/kg姜黄素组,每组5只,均采用腹腔注射给药,分别给予生理盐水及对应剂量姜黄素,每日1次,每次200μL,连续16 d。自给药当天起,隔天观察和记录各组裸鼠体重和瘤体体积;16 d后麻醉裸鼠,分离瘤组织,记录瘤重并计算抑瘤率;采用蛋白免疫印迹法测定瘤组织中内质网应激通路相关蛋白及凋亡相关蛋白的表达水平;采用免疫组织化学法检测瘤体组织中葡萄糖调节蛋白78(GRP78)和需肌醇酶(IRE1)阳性表达水平。结果:不同剂量姜黄素组裸鼠体重增长无显著差异(P>0.05),但50和100 mg/kg姜黄素组裸鼠移植瘤体积生长较对照组和10 mg/kg姜黄素组明显减小(P均<0.05)。10、50和100 mg/kg姜黄素组抑瘤率分别为35.3%、45.7%、54.7%。蛋白印迹结果显示,与对照组相比,50、100 mg/kg姜黄素组GRP78、IRE1、C/EBP同源蛋白(CHOP)以及Cleaved Caspase-3蛋白表达明显增加(P均<0.05),10、50、100 mg/kg姜黄素组p-PERK和p-eIF2α以及Bcl-2蛋白表达明显增加(P均<0.05)。免疫组织化学结果显示,10、50、100 mg/kg姜黄素组瘤组织中GRP78、IRE1蛋白阳性表达均较对照组增加(P均<0.05)。结论:姜黄素可抑制人肝癌SMMC-7721细胞裸鼠移植瘤生长,其机制可能与激活内质网应激通路有关。Objective:To investigate the inhibitory effect of curcumin on the growth of human carcinoma SMMC-7721 cell transplanted tumor in nude mice and its potential mechanism.Methods:Transplanted tumor model of SMMC-7721 cells was established in 20 nude mice,and the tumor-bearing nude mice were equally divided into control group and three different concentrations of curcumin(10,50 and 100 mg/kg)groups,with 5 mice in each group.The mice in each group was intraperitoneally injected with normal saline or corresponding dose of curcumin,once a day,200μL each time,for 16 consecutive days.The body weight and tumor volume of each group were observed and recorded every other day from the day of administration.After 16 days,tumor tissues were harvested and tumor inhibition rates of curcumin treatment groups were calculated by the weighed tumor body.The expression levels of ER stress-related proteins and apoptotic proteins in tumor tissues were analyzed by Western blotting.The positive expressions of glucose requlated protein 78(GRP78)and inositol requiring enzyme 1(IRE1)were analyzed by immunohistochemical staining.Results:Compared with that in the control group,there was no significant difference in the weight gain of nude mice in different doses of curcumin groups(P>0.05),whereas the volume of transplanted tumor in 50 and 100 mg/kg curcumin groups was significantly smaller than that in the control group and 10 mg/kg curcumin group(P<0.05).The tumor inhibition rates of 10,50 and 100 mg/kgcurcumin groups were 35.3%,45.7%and 54.7%,respectively.Western blotting showed that GRP78,IRE1,C/EBP homologous protein(CHOP)and Cleaved caspase-3 protein expressions in 50 and 100 mg/kg curcumin groups were significantly up-regulated compared with that in the control group,and the protein expressions of p-PERK,p-eIF2αand Bcl-2 in 10,50 and 100 mg/kg curcumin groups were higher than those in the control group(both P<0.05).Results of immunohistochemical staining showed that the positive expression of proteins GRP78 and IRE1 in tumor tissues of a

关 键 词：姜黄素 肝癌 内质网应激 未折叠蛋白反应 细胞凋亡 

分 类 号：R735.7[医药卫生—肿瘤]