基于网络药理学方法探讨扶正抑瘤方治疗原发性肝癌的作用机制

To Explore the Mechanism of Fuzheng Anti-Tumor Prescription in the Treatment of Primary Hepatocellular Carcinoma Based on Network Pharmacology Methods

目的:运用网络药理学方法,分析扶正抑瘤方治疗原发性肝癌的作用机制。方法:通过TCMSP数据库查询扶正抑瘤方中4味药的有效成分及对应的靶点。通过Genecard数据库收集原发性肝癌的相关靶点,并与药物的靶点进行匹配,获得交集靶点。将交集靶点导入String数据库中绘制蛋白互作图,并通过Cytoscape3.8.2对PPI图进行可视化分析,找出关键靶点。建立Excel表,利用Cytoscape3.8.2及插件Cytohubba筛选出扶正抑瘤方中主要活性成分。通过R软件对关键靶点进行GO分析和KEGG通路富集分析,在Cytoscape3.8.2中绘制药物–靶点–疾病–靶点网络图。结果:共收集到扶正抑瘤方的有效成分14个,相关的靶点694个,疾病靶点8803个,交集靶点184个,从中筛选出Degree值较高的作为蛋白相互作用中的关键靶点共5个(JUN, IL6, AKT1, CXCL8, CDKN1A)。筛选出度值排列在前3位的活性成分,依次是槲皮素、豆甾醇和β-谷甾醇。经过GO分析得到2457个生物学过程,经过KEGG富集分析,得到106条信号通路,包括AGE-RAGE信号通路、PI3K-ART信号通路、MAPK信号通路、IL-17信号通路、TNF信号通路等。讨论:扶正抑瘤方治疗原发性肝癌具有多成分、多靶点,多途径的特点,筛选的关键靶点和主要通路为阐明治疗原发性肝癌的作用机制提供了科学依据。

Objective: To analyze the mechanism of Fuzheng anti-tumor prescription in the treatment of pri-mary hepatocellular carcinoma by network pharmacology method. Methods: The active compo-nents and corresponding targets of four drugs in Fuzheng anti-tumor prescription were queried through TCMSP database. Related targets of primary liver cancer were collected from Genecard da-tabase and matched with drug targets to obtain intersection targets. The intersection targets were imported into the String database to draw the protein interaction map, and the PPI map was visu-alized and analyzed by Cytoscape3.8.2 to identify the key targets. Build Excel table, Cytoscape3.8.2 and Cytohubba were used to screen out the main active ingredients in Fuzheng anti-tumor pre-scription. GO analysis and KEGG pathway enrichment analysis of key targets were performed by R software, and drug-target-disease-target network map was drawn in Cytoscape3.8.2. Results: A total of 14 active components, 694 related targets, 8803 disease targets, and 184 intersection targets were collected. Among them, 5 key targets (JUN, IL6, AKT1, CXCL8, CDKN1A) with higher degree were selected as the key targets in protein interaction. The top 3 active ingredients were quercetin, stigmasterol and β-sitosterol. After GO analysis, 2457 biological processes were obtained, and after KEGG enrichment analysis, 106 signaling pathways were obtained, including AGE-RAGE signaling pathway, PI3K-ART signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF sig-naling pathway, etc. Conclusion: Fuzheng anti-tumor prescription has the characteristics of mul-ti-component, multi-target and multi-pathway in the treatment of primary liver cancer. The key targets and main pathways screened provide a scientific basis for elucidating the mechanism of ac-tion in the treatment of primary liver cancer.