葛根芩连汤治疗结直肠癌的潜在靶点及作用机制研究  

The potential target and mechanism of action in the treatment of colorectal cancer

作　　者：蔡蓉[1] 周燕萍[1] 张金金 胡作为[1,2] CAI Rong;ZHOU Yan-ping;ZHANG Jin-jin;HU Zuo-wei(Hubei University of Chinese Medicine,Wuhan 430061;Wuhan No.1 Hospital,Department of Oncology,Wuhan 430022)

机构地区：[1]湖北中医药大学,430061 [2]武汉市第一医院,430022

出　　处：《现代消化及介入诊疗》2022年第9期1129-1140,共12页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：湖北省教育厅科学研究计划项目(B2019096);湖北中医药大学校级科研基金(2022ZZXQ032)。

摘　　要：目的 采用网络药理学方法探讨葛根芩连汤治疗结直肠癌(CRC)的靶点和机制,通过生物信息学分析,验证CRC与邻近正常组织之间潜在靶基因的表达及预后关系。方法 利用TCMSP预测葛根芩连汤的化学成分及相关作用靶点,结合GeneCards, OMIM以及CTD数据库筛选与CRC疾病的共同靶点,通过Cytoscape软件构建药物-活性成分-疾病-靶点互作网络,并采用R软件进行GO富集和KEGG通路分析。最后,分别通过TCGA数据库和ROC、模型构建和评估的临床统计等验证了靶基因的差异表达和预后分析。结果 共收集葛根芩连汤与CRC的共同靶点153个,其中核心化合物有黄芩素、槲皮素、半枝莲素、豆甾醇等,MMP3、ALB、AKT1、VEGFA、IL1B等可作用葛根芩连汤抗结直肠癌的核心靶点。GO富集分析共得到430条结果,主要富集在G蛋白偶联神经递质受体活性,神经递质受体的活动,G蛋白偶联受体信号通路,偶联环核苷酸第二信使等。KEGG通路分析共得到72条通路,涉及Toll样受体信号通路,钙信号通路多条经典的炎症及肿瘤调节通路等。通过ROC分析探索hub genes,以及预后分析,发现MMP3在TNM分期和风险预后模型都具有统计学意义。结论 结直肠癌中MMP3、ALB、AKT1、VEGFA、IL1B等差异表达是葛根芩连汤治疗CRC的潜在治疗靶点,通过影响Toll样受体信号通路,钙信号通路等多条信号传导发挥治疗结直肠癌的作用,体现了中药多成分-多靶点-多途径的作用特点。Objective To explore the target and mechanism of Gegenqinlian Decoction in the treatment of colorectal cancer(CRC) by network pharmacology, and to verify the relationship between the expression of potential target genes and prognosis between CRC and adjacent normal tissues by bioinformatics analysis. Methods Gegenqinlian Decoction chemical ingredients and related targets were predicted by public databases(TCMSP).Combining GeneCards, OMIM and CTD database screening for common targets with CRC disease, a drug-active component-disease-target interaction network was constructed by Cytoscape software, and GO enrichment and KEGG pathway analysis. Finally, the differential expression and prognostic analysis of target genes were validated by clinical statistics from the TCGA database and ROC, model construction and evaluation, respectively. Results A total of 153 common targets of pueraria soup and CRC were collected, among which the core compounds were baicalein, quercetin, hemislin, dousterol, etc., and MMP3, ALB, AKT1, VEGFA, IL1B could serve the core targets of pueraria soup against colorectal cancer.GO enrichment analysis yielded 430 results, mainly enriched in G protein-coupled neurotransmitter receptor activity, neurotransmitter receptor activity, G protein-coupled receptor signaling, coupled loop nucleotide second messenger, et al. The KEGG pathway analysis yielded 72 pathways involving Toll-like receptor signaling, and multiple classic inflammatory and tumor regulatory pathways of calcium signaling.Exploring hub genes, as well as prognostic analysis revealed that MMP3 was statistically significant in both TNM staging and risk prognostic models. Conclusion This study reveals that the differential expression of MMP3, ALB, AKT1, VEGFA, IL1B and other cells in colorectal cancer is a potential therapeutic target for the treatment of CRC. It affects the number of Toll-like receptor signaling and calcium signaling to play a role in treating colorectal cancer, which reflects the characteristics of multi-component-multi-

关 键 词：葛根芩连汤 网络药理学 生物信息学 结直肠癌 MMP3 作用机制 

分 类 号：R285.5[医药卫生—中药学] R735.3[医药卫生—中医学] R574