人参皂苷Rg3通过内质网应激PERK通路抑制人胆囊癌裸鼠移植瘤生长的研究  

Ginsenoside Rg3 inhibit growth of human gallbladder carcinoma GBC-SD cells in nude mice by PERK pathway activation of endoplasmic reticulum stress

作　　者：黄捷[1] 吴可人[1] 徐涛[1] 金法[1] 叶志鹏[1] 阎九亮[1] 李宁[1] HUANG Jie;WU Keren;XU Tao(Department of Hepatobiliary Surgery,the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China)

机构地区：[1]浙江中医药大学附属第一医院肝胆外科,杭州310006

出　　处：《浙江医学》2018年第22期2415-2418,共4页Zhejiang Medical Journal

基　　金：浙江省自然科学基金资助项目(LY17H290008);浙江省医药卫生科技计划项目(2018KY558)

摘　　要：目的探讨人参皂苷Rg3通过内质网应激双链RNA依赖性蛋白激酶样内质网激酶(PERK)通路抑制人胆囊癌裸鼠移植瘤生长的机制。方法采用随机数字表法将裸鼠分为人参皂苷Rg3灌胃组和对照组各6只,于每只裸鼠右侧腹股沟皮下注射0.2ml细胞悬液(1×10~6/个人胆囊癌细胞GBC-SD),7d后观察成瘤情况。待肿瘤长至50～70mm^3开始进行灌胃处理。人参皂苷Rg3组将Rg3按20mg/kg剂量溶于0.2ml 0.9%氯化钠溶液后灌胃,对照组用0.2ml 0.9%氯化钠溶液灌胃,1次/d,连续给药3周。以游标卡尺测量肿瘤长、短径,计算肿瘤体积。实验结束时,处死小鼠,切除肿瘤并称重。采用Western blot法检测磷酸化PERK(p-PERK)、PERK、真核起始因子2α(eIF2α)、磷酸化eIF2α(p-eIF2α)、转录激活因子4(ATF4)、脂质运载蛋白2(Lcn2)蛋白表达水平。结果人参皂苷Rg3灌胃组瘤体质量明显低于对照组,差异有统计学意义(P<0.01)。灌胃12d开始,人参皂苷Rg3灌胃组裸鼠瘤体积较对照组均明显减小,差异均有统计学意义(均P<0.01)。人参皂苷Rg3灌胃组p-PERK、p-elF2α、ATF4和Lcn2蛋白表达水平均明显高于对照组,差异均有统计学意义(均P<0.01);但两组PERK和elF2α蛋白表达水平比较差异均无统计学意义(均P>0.05)。结论人参皂苷Rg3通过激活胆囊癌细胞内质网应激PERK通路,抑制人胆囊癌裸鼠移植瘤生长。Objective To investigate the effect of ginsenoside Rg3 on growth of transplanted human gallbladder carcinoma in nude mice and its mechanism. Methods Nude mice were randomly divided into two groups： the Rg3 group and the control group（n=6/group）. GBC-SD cells（1×106/mouse） mixed with PBS （200μl/mouse） were inoculated into the right inguen of mice. When the tumors reached a volume of 50-70mm3, mice were given a daily oral dose of 20mg/kg Rg3 or vehicle （200μl saline, control group） for 21 days. Tumor dimensions were measured every 3 days using a digital caliper, and tumor volume was calculated using the formula： V = length×width2×0.5. At the end of the experiment, the mice were sacrificed and the tumors were removed and weighed. Tumor xenografts were harvested and Western blot was performed to detect the expression of p-PERK, PERK, elF2α, p-elF2α, ATF4 and Lcn2 proteins in tumor tissues. Results The tumor growth of the Rg3 group was significantly slower than those of control group（P〈0.01）. From the 12th day after gastric administration, the volume of the tumor was significantly lower than those of control group（all P〈0.01）. The expressions of p-PERK, p-elF2α, ATF4 and Lcn2 in Rg3 group was significantly higher than that in the control group（all P〈0.01）. Conclusion Ginsenoside Rg3 can inhibit the growth of transplanted human gallbladder carcinoma in node mice by PERK pathway activation of endoplasmic reticulum stress.

关 键 词：人参皂苷RG3 胆囊癌 内质网应激 PERK通路 

分 类 号：R285.5[医药卫生—中药学]