基于网络药理学探讨大补脾汤治疗肝癌的作用机制

Study on the Mechanism of Dabupi Decoction in the Treatment of Liver Cancer Based on Network Pharmacology

目的利用网络药理学的方法,建立大补脾汤的活性成分-作用靶点-通路的网络图,对作用靶点的基因功能和通路进行富集分析,从而探讨大补脾汤治疗肝癌的可能作用机制。方法通过TCMSP数据库、中国台湾中医药资料库获得大补脾汤主要活性成分。采用Swiss Target Prediction预测活性成分的潜在靶点,并与肝癌疾病靶点数据进行比对,获得大补脾汤治疗肝癌的作用靶点。采用DAVID数据库平台对作用靶点的GO注释和KEGG通路进行富集分析和蛋白功能归属。最后通过Cytoscape构建大补脾汤治疗肝癌的"活性成分-作用靶点-通路"网络图。结果大补脾汤潜在的有效成分共有118个,其中人参、甘草、旋覆花含有65种成分可能具有治疗肝癌的作用。大补脾汤治疗肝癌的可能靶点共29个,其中EGFR、SRC、PTGS2、MMP9、MMP2、MCL1、MET、AR和ESR1等可能为关键靶点基因,涉及到对微小RNAs、雌激素受体通路、肿瘤相关通路等的调控作用。结论大补脾汤中山奈酚、槲皮素、木犀草素等可能通过调控微小RNAs和雌激素信号通路等机制,作用于EGFR、ESR1、SRC、MET等靶点发挥治疗肝癌的作用,为大补脾汤药效机制的多角度研究和肝癌的中医药治疗提供思路。

Objective Using the method of network pharmacology,author explored the possible mechanism of Dabupi Decoction in the treatment of liver cancer.Methods The main active components of Dabupi Decoction were obtained from TCMSP database and Taiwan(China) Traditional Chinese medicine database.SWISS-target prediction was used to predict the potential target of the active ingredients,and compared with the target data of liver cancer disease to obtain the target of Dabupi Decoction in the treatment of liver cancer.GO annotation and KEGG pathway were enriched and analyzed by David database platform.Finally,the network diagram of active component-target-pathway of Dabupi Decoction in the treatment of liver cancer was constructed by Cytoscape.Results There were 118 potential active ingredients in Dabupi Decoction,among which there were 65 ingredients in Radix Ginseng,Radix Glycyrrhizae and Flos Inulae which may have therapeutic effect on liver cancer.Also,we predicted 29 possible target genes in the treatment of liver cancer with Dabupi Decoction,and EGFR,SRC,PTGS2,MMP9,MMP2,MCL1,MET,AR and ESR1 may be the key target genes,which were involved in the regulation of microRNAs,Estrogen signaling pathway and tumor-related pathway.Conclusion Kaempferol,Quercetin and Luteolin in Dabupi Decoction may act on EGFR,ESR1,SRC,MET and other targets in the treatment of liver cancer through the regulation of microRNAs and Estrogen signaling pathways.This study provides an idea for the multi-angle study of the pharmacodynamic mechanism of Dabupi Decoction and the treatment of liver cancer with traditional Chinese medicine.