基于网络药理学和蛋白质组学探讨加减血癥汤对浸润型胃癌的作用  

The potential mechanism of Jiajian Xuezheng Decotion in infiltrative gastric cancer through on network pharmacology and proteomics

作　　者：章立华 卓慧钦[1,3] 侯静静 章惠萍 周阳 蔡建春 Zhang Lihua;Zhuo Huiqin;Hou Jingjing;Zhang Huiping;Zhou Yang;Cai Jianchun(Department of Gastrointestinal Surgery,Zhongshan Hospital Xiamen University,Xiamen 361004,China;Institute of Gastrointestinal Oncology,Medical College of Xiamen University,Xiamen 361004,China;Xiamen Municipal Key Laboratory of Gastrointestinal Oncology,Xiamen 361004,China;The Third Clinical School,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]厦门大学附属中山医院胃肠外科,厦门361004 [2]厦门大学医学院胃肠肿瘤研究所,厦门361004 [3]厦门市胃肠肿瘤重点实验室,厦门361004 [4]广州中医药大学第三临床医学院,广州510006

出　　处：《国际中医中药杂志》2022年第10期1150-1156,共7页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81871979,81372616);福建省自然科学基金项目(2021J02056,2021J05276);厦门市医疗卫生指导性项目(3502Z20199171,3502Z20204002)。

摘　　要：目的通过网络药理学和蛋白质组学方法探讨加减血癥汤治疗浸润型胃癌的潜在作用机制。方法利用TCMSP检索加减血癥汤有效成分及其作用靶点,采用高效液相色谱法串联质谱联用(HPLC-MS/MS)法测定浸润型胃癌的靶点,加减血癥汤预测的靶基因与浸润型胃癌的靶点蛋白质数据进行维恩分析,获取作用靶基因,通过STRING获得蛋白质-蛋白质相互作用网络(PPI),采用Cytoscape软件构建方剂-药物-化合物-基因网络,通过DAVID数据库对靶点进行GO富集分析和KEGG通路富集分析。结果筛选出加减血癥汤中69个有效成分,215个药物靶点;660个在浸润型胃癌过表达蛋白质,10个药物靶点和基因靶点的共有靶点。PPI网络包括10个蛋白节点,其中3个核心节点为CASP3、BCL2L1和STAT1。KEGG富集到11条通路,包含PI3K-Akt信号通路、p53信号通路、癌症中蛋白聚糖、细胞凋亡、Jak-STAT信号通路等。结论加减血癥汤可能通过PI3K-Akt信号通路、p53信号通路和Jak-STAT信号通路介导凋亡发挥抑制作用。本研究为加减血癥汤治疗浸润型胃癌作用机制的进一步研究提供理论依据。Objective To explore the potential mechanism of Jiajian Xuezheng Decotion in infiltrative gastric cancer by network pharmacology and proteomics.Methods The Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)database was used to find the compounds and their targets of Jiajianxuezhengtang,and the targets of invasive gastric cancer were determined by high performance liquid chromatography with tandem mass spectrometry(HPLC-MS/MS).The predicted target gene of Jiajian Xuezheng Decotion and the target protein data of infiltrative gastric cancer were analyzed by Venny to obtain the target gene.The target gene set was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment by the David.The protein interaction network diagram(PPI)was obtained by the String method,displaying the prescription-drug-compound-gene network in Cytoscape software.Results 69 active ingredients and 215 drug targets were screened from Jiajian Xuezheng Decotion;660 proteins were significantly up-expressed in infiltrative gastric cancer,and 10 drug targets and gene targets were the common targets.There were 10 protein nodes in the PPI network,of which 3 core nodes were CASP3,BCL2L1 and STAT1.The 11 KEGG pathways were significantly enriched such as include PI3K-Akt signaling pathway,p53 signaling pathway,proteoglycan in cancer,apoptosis,Jak-STAT signaling pathway and other pathways.Conclusions Jiajian Xuezheng Decotion plays an anti-infiltrative gastric cancer effect possibly regulated apoptosis through PI3K-Akt signaling pathway,p53 signaling pathway and Jak-STAT signaling pathway.This study provides a theoretical basis for further research on the mechanism of Jiajian Xuezheng Decotion in the treatment of invasive gastric cancer.

关 键 词：蛋白质组学 浸润型胃癌 加减血癥汤 有效成分 网络药理学 药理作用分子作用机制(中药) 

分 类 号：R285[医药卫生—中药学]