基于网络药理学探讨穿心莲治疗乳腺癌的作用机制

Molecular mechanism of Andrographis herba for breast cancer based on network pharmacology

目的基于网络药理学探讨穿心莲治疗乳腺癌的作用靶点及潜在作用机制。方法采用TCMSP分析穿心莲的化学成分、作用靶点。借助基因组注释(GeneCards)数据库及人类孟德尔遗传(OMIM)数据库,预测和筛选乳腺癌作用靶点,采用Cytoscape 3.7.2软件,构建"活性成分-靶点"网络图,借助String数据库平台构建蛋白质相互作用网络。利用Bioconductor平台和R语言进行GO富集分析和KEGG通路分析。结果筛选得到穿心莲24个有效成分,治疗乳腺癌的作用靶点有71个,乳腺癌疾病靶点共13 234个。穿心莲-乳腺癌共同靶点51个,位列前5的靶点有P53蛋白、IL-6、氨基端激酶(JUN)、G1/S-特异性周期蛋白-D1(CCND1)、雌激素受体α(ERS1),穿心莲-乳腺癌KEGG富集的通路是雌激素受体通路、P53信号通路、Notch信号通路、Wnt信号通路。结论 TP53、ERS1、CCND1等靶点可能是穿心莲治疗乳腺癌的关键靶点,通过调控雌激素受体通路、P53信号通路等信号通路发挥抗乳腺癌作用。本研究为穿心莲治疗乳腺癌作用机制的深入研究提供了理论依据。

Objective Based on the methodology of network pharmacology,this study preliminarily predicted the major targets and pathways of Andrographis herba in the treatment of breast cancer.Methods The active components of Andrographis herba were screened by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP);breast cancer targets were predicted and screened by Genecard database platform and OMIM database platform;active ingredient-targets networks were built by Cytoscape(3.7.2)software,and protein interaction networks were built by String database platform.Finally,Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed by using Bioconductor platform and R language.Results A total of 24 active ingredients of Andrographis herba and 13234 targets for breast cancer were obtained,involving 71 targets related to Andrographis herba.There were 51 common targets for Andrographis herba-breast cancer.The top five targets are TP53,IL6,JUN,CCND1,and ERS1.Andrographis herba-breast cancer KEGG-enriched pathways are estrogen signaling pathway,P53 signaling pathway,Notch signaling pathway,and Wnt signaling pathway.Conclusions The TP53,ERS1,and CCND1 and other targets may be the key targets for Andrographis herba paniculata to treat breast cancer.It plays an anti-breast cancer effect by regulating the signal pathways such as the estrogen receptor pathway and the P53 signaling pathway.This paper provides a theoretical basis for further exploration of the mechanism research of Andrographis herba in the treatment of breast cancer.