基于网络药理学六君子汤治疗胃癌的物质基础与作用机制研究

Network Pharmacology-based Study on Material Basis and Mechanism of Liujunzi Decoction for Gastric Cancer Treatment

关键词:  六君子汤  胃癌  活性成分  靶点  通路

Key words:  Liujunzi decoction  gastric cancer  active ingredients  targets  pathways

摘要:

目的 探讨六君子汤治疗胃癌的药效物质基础与潜在的作用机制。方法 依托TCMSP和TCM-MESH数据库平台对六君子汤中的活性成分进行检索和筛选；利用SwissTargetPrediction，TTD，CTD，GeneCards等数据库对六君子汤活性成分以及胃癌相关靶点进行预测和筛选，进而构建活性成分-靶点网络图。对得到的靶点通过STRING进行蛋白互作（protein-protein interaction，PPI）网络构建并筛选核心靶点，进而通过ONCOMINE数据库分析核心靶点在胃癌中的表达。利用DAVID在线数据库对靶点进行基因本体论（gene ontology，GO）和KEGG通路富集分析以探讨靶点的生物学意义。对于得到的活性成分，作用于胃癌的靶点以及所富集的通路，构建六君子汤成分-靶点-通路网络图。结果 从六君子汤中筛选得到21个活性有效成分和43个作用于胃癌的相关靶点。靶点的PPI网络分析得到6个核心靶点，在ONCOMINE数据库的胃癌样本和正常样本中均存在显著的表达差异。对靶点的GO和KEGG通路富集分析结果显示这些靶点富集在生物过程的条目有74个，细胞组分的有9个，分子功能的有15个，而富集的KEGG通路有78条，涉及肿瘤、信号通路、病毒致癌、凋亡、癌症中的蛋白多糖等多种与胃癌密切相关的通路。六君子汤成分-靶点-通路网络图揭示了六君子汤中的药效物质和作用靶点，以及靶点与疾病通路之间的互作关系。结论 本研究初步明确了六君子汤通过多成分-多靶点-多通路治疗胃癌的作用机制，为深入研究六君子汤的药效物质基础和作用机制奠定基础。

Abstract:

OBJECTIVE To explore the material basis and underlying mechanism of Liujunzi decoction for gastric cancer(GC) treatment. METHODS Active chemical ingredients in Liujunzi decoction were searched based on the TCMSP and TCM-MESH database, the ingredients related and GC related targets were screened from the SwissTargetPrediction, TTD, CTD, GeneCards database. The protein-protein interaction(PPI) network of the targets were performed to search out the core targets, subsequently, the ONCOMINE database were applied to analysis the expression of these core targets in GC. After then, the DAVID online tool was used to perform the gene ontology and KEGG pathway analysis for the targets. For the obtained active ingredient, acting on the target of gastric cancer and the enriched pathway, ingredients-targets-pathways network of Liujunzi decoction was constructed. RESULTS The 21 active ingredients and 43 related targets for GC treatment were screened out from the Liujunzi decoction. PPI network analysis of the target obtained 6 core targets, and there were significant differences in expression between the gastric cancer samples and the normal samples in the ONCOMINE database. The GO and KEGG pathway enrichment analysis of the target showed that there were 74 entries in the biological process, 9 in the cellular component, 15 in the molecular function, and 78 in the enriched KEGG pathway. Involved tumors, signaling pathways, viral carcinogenesis, apoptosis, proteoglycans in cancer, and other pathways closely related to GC. Ingredients-targets-pathways network of Liujunzi decoction revealed the complex and closely interactions among the active ingredients, targets and pathways. CONCLUSION The result of the study preliminarily verified the mechanisms of Liujunzi decoction for GC through multi-ingredients, multi-target and multi-pathway interactions, and lay foundation for further studies on the material basis and mechanism of action.