基于网络药理学的“蒲公英-夏枯草”药对治疗乳腺癌作用机制研究

Research on the Mechanism of “Dandelion-Selfheal”in Treatment of Breast Cancer Based on Network Pharmacology

目的:基于网络药理学方法,探讨"蒲公英-夏枯草"药对治疗乳腺癌作用机制。方法:利用中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选出"蒲公英-夏枯草"药对的主要化学成分及作用靶点,建立"成分-靶点"蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络。利用比较毒理基因组学数据库(comparative toxicogenomics database,CTD)检索与乳腺癌相关的基因,采用Cytoscape 3. 6. 1软件构建"疾病-靶点"PPI网络。基于Cytoscape 3. 6. 1软件的Merge功能,合并"成分-靶点"和"疾病-靶点"的PPI网络,筛选出主要核心网络,借助David数据库、Reactome数据库及Omicshare平台,进行基因本体(gene ontology,GO)富集分析、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。通过动物实验,验证"蒲公英-夏枯草"药对的抗肿瘤作用机制。结果:筛选得到含383个节点、594条连接的"蒲公英-夏枯草"药对"成分-靶点"PPI网络,含500个靶点的乳腺癌"疾病-靶点"PPI网络。利用网络合并,最终建立了含61个核心靶点的"成分-靶点-疾病"网络。基因GO功能分析结果主要与生物过程和分子功能有关;基因KEGG通路富集分析结果与免疫系统、性激素分泌以及肿瘤细胞增殖与凋亡有关。动物实验结果显示,"蒲公英-夏枯草"药对能提高乳腺癌模型小鼠白细胞介素6水平,抑制乳腺癌细胞增殖,促进乳腺癌细胞凋亡。结论:"蒲公英-夏枯草"药对治疗乳腺癌的可能机制与调节免疫系统、性激素分泌以及肿瘤细胞增殖与凋亡有关。

OBJECTIVE: To probe into the mechanism of "dandelion-selfheal"in treatment of breast cancer based on network pharmacology. METHODS: To screen the main chemical component and target spot of the herbal pair of "dandelion-selfheal"through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP),so as to establish the protein-protein interaction( PPI) network of "component-target". Comparative toxicogenomics database( CTD) was used to retrieve genes related to breast cancer,Cytoscape 3. 6. 1 was adopted to construct "disease-target " PPI network. Based on the Merge function of Cytoscape 3. 6. 1,the PPI networks of "component-target"and "disease-target"were merged to screen out the main core network. With the help of the David database,Reactome database and Omicshare platform, gene ontology( GO) enrichment analysis and Kyoto encyclopedia of genes and genomes( KEGG) pathway enrichment analysis were conducted. Through animal experiments,the anti-tumor mechanism of the herbal pair of "dandelion-selfheal"was verified. RESULTS: A PPI network of "component-target"containing 383 nodes and 594 linked herbal pair of "dandelion-selfheal"and a PPI network of "disease-target"of breast cancer containing 500 target spots were screened out. With utilization of the network merger,a "component-target-disease"network containing 61 core targets was finally established. The result of gene GO function analysis was mainly related to biological process and molecular function;the result of gene KEGG pathway enrichment analysis was related to immune system,sex hormone secretion,proliferation and apoptosis of tumor cell. The result of animal experiment showed that the herbal pair of "dandelion-selfheal"can increase the IL-6 level,inhibit the proliferation of breast cancer cells and promote the apoptosis of breast cancer cells in model mice.CONCLUSIONS: The possible mechanism of herbal pair of"dandelion-selfheal"in treatment of breast cancer is related to immune system regulation,sex hormone secretion,tumor cell proliferation and apoptosis.