Mechanism of Action of the Traditional Chinese Medicine Formula Weichang’an in the Treatment of Gastric Cancer Based on TMT Proteomics Analysis  

基于TMT蛋白质组学分析中药复方胃肠安治疗胃癌的作用机制

作　　者：Yaofei Niu Weixia Chen Yajie Ding Yan Xu Aiguang Zhao 牛垚飞;陈伟霞;丁亚杰;徐燕;赵爱光(河南省人民医院,河南郑州450003;上海中医药大学附属龙华医院,上海200062;河南省中医院/河南中医药大学第二附属医院,河南郑州450000)

机构地区：[1]Department of Infection,Henan Provincial People’s Hospital,Zhengzhou,Henan,China [2]Department of Oncology,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China [3]Department of Oncology,Henan Province Hospital of TCM(The Second Affiliated Hospital of Henan University of Chinese Medicine),Zhengzhou,Henan,China

出　　处：《Chinese Medicine and Natural Products》2024年第4期173-181,共9页中医学报(英文)

基　　金：funded by the Special Research Project of Traditional Chinese Medicine in Henan Province(2022ZY2031).

摘　　要：Objective The aim of the study was to screen key proteins involved in the treatment of human gastric cancer subcutaneous xenografts in nude mice by the traditional Chinese medicine formula Weichang’an and to explore its mechanism of action in treating gastric cancer.Methods Sixteen 7-to 8-week-old female BALB/C nude mice were used to establish a human gastric cancer subcutaneous xenograft model by bilateral axillary injection of MKN45 cells.Mice with successfully established tumors were randomly divided into the Weichang’an group and the model group,with eight mice in each group.Mice in the Weichang’an group were orally administered 0.5mL of Weichang’an decoction,while mice in the model group were given 0.5 mL of normal saline by gavage once a day for 21 consecutive days.On day 28,the animals were sacrificed by cervical dislocation,and tumors were excised to measure tumor weight and assess the tumor suppression rate.Tandem mass tags(TMT)quantitative proteomics was used to analyze the tumor samples,identify differentially expressed proteins,and perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Compared with the model group,the tumor weight in the Weichang’an group was significantly reduced(p<0.001),and the tumor suppression rate was 41.40%,indicating that Weichang’an can inhibit the growth of human gastric cancer subcutaneous xenografts in nude mice.TMT quantitative proteomics identified a total of 2,856 proteins,with 13 proteins showing downregulated expression and 25 proteins showing upregulated expression in the Weichang’an group.GO enrichment analysis revealed that differentially expressed proteins were mainly enriched in cellular components such as the cell membrane,extracellular matrix,and envelope,and participated in biological processes like negative regulation of cell adhesion hematopoiesis,and skeletal system development,with functions in cell adhesion molecule binding and molecular sensor activity.The KEGG pathway enrichment analy目的:筛选胃肠安治疗人胃癌裸鼠皮下移植瘤的关键蛋白,探索胃肠安治疗胃癌的作用机制。方法:16只7~8周龄雌性BALB/C裸鼠16只,双侧腋下注射MKN45细胞建立人胃癌裸鼠皮下移植瘤模型。将模型建立成功的裸鼠随机分为胃肠安组和模型组,每组各8只,胃肠安组小鼠灌胃胃肠安水煎液0.5mL,模型组小鼠灌胃生理盐水0.5mL,每日1次,共21天。实验第28天,颈椎脱臼处死动物取出瘤体检测瘤体质量并评估胃肠安的抑瘤率。TMT定量蛋白组学对干预后的瘤体进行分析,筛选差异蛋白,并对差异蛋白质进行基因本体论(gene ontology,GO)和京都基因与基因组(Kyoto encyclopedia of genes and genomes,KEGG)代谢通路富集分析。结果:与模型组相比,胃肠安组裸鼠瘤体质量显著降低(P<0.001),且抑瘤率为41.40%,表明胃肠安可抑制人胃癌裸鼠皮下移植瘤生长。TMT定量蛋白组学共鉴定到2856个蛋白质,其中13个蛋白在胃肠安组中表达水平下调,25个蛋白在胃肠安组中表达水平上调。GO富集分析发现,差异表达蛋白主要富集在细胞膜、细胞外基质、包膜等细胞成分上,参与细胞黏附负调节、造血功能和骨骼系统的发发育等生物学过程,发挥细胞黏附分子结合、分子传感器活动等功能。KEGG富集的信号通路为自噬溶酶体通路。结论:胃肠安可通过调控多种蛋白表达及自噬-溶酶体通路信号通路发挥治疗胃癌的作用。

关 键 词：TMT proteomics Weichang’an gastric cancer differentially expressed protein 

分 类 号：R73[医药卫生—肿瘤]