涤痰荡瘤汤调节ERK2/ETS1/MMP9通路抑制裸鼠胃癌移植瘤生长  

Ditan Dangliu Prescription Inhibits the Growth of Gastric Cancer Xenografts in Nude Mice by Regulating ERK2/ETS1/MMP9 Pathway

作　　者：孙琪[1,2] 王华[1] 郭维 SUN Qi;WANG Hua;GUO Wei(Institute of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan 750004,China;Key Laboratory of Ningxia Ethnomedicine Modernization,Ministry of Education,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学中医学院,银川750004 [2]宁夏少数民族医药现代化教育部重点实验室,银川750004

出　　处：《宁夏医科大学学报》2021年第5期536-541,546,共7页Journal of Ningxia Medical University

基　　金：宁夏高等教育科学研究项目(NGY2018-72);宁夏高等学校一流学科建设(中医学学科)资助项目(NXYLXK2017A06)。

摘　　要：目的探讨涤痰荡瘤汤对人胃癌细胞裸鼠胃原位移植瘤的抑瘤作用及其对microRNA-506-3p和胞外信号调节激酶2(ERK2)/E26转录因子1(ETS1)/基质金属蛋白酶9(MMP9)信号通路的影响。方法培养人胃癌细胞系MKN45、BCG823并分别构建人胃癌细胞裸鼠原位移植瘤模型,两种模型均随机分为中药组(涤痰荡瘤汤)、西药组(5-FU)、空白组(生理盐水)。饲养6周后处死荷瘤鼠剥离瘤体称重计算抑瘤率,并观察肿瘤转移情况。qPCR和Western blot分别检测各组肿瘤组织中microRNA-506-3p、ETS1、ERK2、MMP9的mRNA及蛋白表达。结果MKN45肿瘤组织中,中药组和西药组抑瘤率分别为45.1%和60.4%,BCG823肿瘤组织中,中药组和西药组抑瘤率分别为51.1%和66.6%。qPCR检测结果显示:在MKN45、BCG823移植瘤中,与空白组比较,中药组和西药组microRNA-506-3p表达上调(P均<0.01),ERK2、ETS1表达均降低(P均<0.01);与西药组比较,中药组microRNA-506-3p表达降低(P<0.01),ERK2、ETS1表达升高(P均<0.01);在MKN45移植瘤中三组MMP9的表达差异无统计学意义(P>0.05),在BCG823移植瘤中,西药组和中药组均低于空白组,且西药组低于中药组(P均<0.01)。Western blot检测结果显示:在MKN45、BCG823移植瘤中,与空白组比较,中药组和西药组中ERK2、ETS1及MMP9表达降低(P均<0.01),中药组ERK2、ETS1及MMP9表达高于西药组(P均<0.01)。结论涤痰荡瘤汤能抑制人胃癌细胞裸鼠胃原位移植瘤增殖,其机制可能通过上调microRNA-506-3p从而下调ERK2、ETS1、MMP9表达而起效。Objective To explore the anti-tumor effect of Ditan Dangliu Prescription against human gastric cancer cell nude mice with orthotopic transplantation tumor through microRNA-506-3p and ERK2/ETS1/MMP9 signal pathway.Methods Human gastric cancer cell lines MKN45 and BCG823 were cultivated and transplanted into nude mice were established and mice with tumor were randomly divided into Chinese Medicine Section(Ditan Dangliu Prescription),Western Medicine Section(5-FU)and Control Section(Normal saline).After 6 weeks of feeding,mice with tumor were killed.Then the tumor was stripped,the anti-tumor rate was computerized and the transplantation of the tumor was observed.Real-time fluorescence quantitative PCR was adopted to test the expression of microRNA-506-3p,mRNA of ETS1,ERK2 and MMP9 in the tumor tissue.Western blot was used to test the protein of ETS1,ERK2 and MMP9 in the tumor tissue.Results The anti-tumor rate of the Western Medicine Section and Chinese Medicine Section were 60.4%and 45.1%in MKN45 cells,66.6%and 51.1%in BCG823 cells.qPCR results showed that in the comparison with Control Section,the expression of microRNA-506-3p was up-regulated in Chinese Medicine Section and Western Medicine Section(P all<0.01),while the expressions of ERK2 and ETS1 were down-regulated(P all<0.01).In the comparison with Chinese Medicine Section the expression of microRNA-506-3p in Western Medicine Section was up-regulated(P<0.01),while the expression of ERK2 and ETS1 were down-regulated(P all<0.01).Regarding the expression of MMP9,there was no difference in the expression of MKN45 transplanted tumors among the three sections(P>0.05),while in BCG823 transplanted tumors,the expressions were lower in the Chinese and Western medicine sections than that in the control section and the Western medicine section was lower than the Chinese medicine section(P all<0.01).Western blot results showed that in the comparison with Control Section,the expressions of ERK2,ETS1 and MMP9 in Chinese Medicine Section and Western Medicine Section were dow

关 键 词：胃癌 microRNA-506-3p 涤痰荡瘤汤 MKN45 BCG823 

分 类 号：R289.1[医药卫生—方剂学] R735.2[医药卫生—中药学]