基于网络药理学和生物信息学方法的白藜芦醇治疗三阴性乳腺癌的机制研究

Network Pharmacology and Bioinformatics-based Study on Mechanism of Resveratrol Against Triple Negative Breast Cancer

关键词:  白藜芦醇  三阴性乳腺癌  网络药理学  靶点  富集分析

Key words:  resveratrol  triple negative breast cancer  network pharmacology  targets  enrichment analysis

摘要:

目的 探索白藜芦醇抗三阴性乳腺癌（triple negative breast cancer，TNBC）的潜在作用机制。方法 利用PharmMapper、SwissTargetPrediction、SuperPred、DrugBank数据库，筛选整合白藜芦醇可能作用的靶点。与CTD、DisGeNET、MalaCards数据库中筛选得到的TNBC靶点相映射后得到白藜芦醇抗TNBC可能作用的靶点。利用DAVID数据库对得到的靶点进行基因功能（Gene ontology，GO）和京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路注释分析，利用STRING数据库和Cytoscape软件构建靶点间的蛋白互作网络，筛选出核心靶点及核心模块。结果 共筛选得到422个白藜芦醇可能作用的靶点，1 799个TNBC相关靶点，映射后共得到白藜芦醇治疗TNBC的潜在作用靶点130个，并从中进一步筛选出了10个核心基因（MAPK1、MAPK3、TP53、SRC、PIK3CA、AKT1、PIK3R1、MAPK8、PTPN11、JAK2），KEGG通路富集提示核心基因主要涉及PI3K-Akt等信号通路。结论 白藜芦醇可能是通过靶向作用于多个靶点及通路，形成相互协调的作用网络从而发挥抗TNBC作用，其中PI3K/Akt通路可能发挥重要作用，为白藜芦醇在TNBC治疗方面的进一步研究提供参考。

Abstract:

OBJECTIVE To explore the potential mechanism of resveratrol against triple negative breast cancer(TNBC). METHODS Databases of PharmMapper, SwissTargetPrediction, SuperPred and DrugBank were used to screen and integrate the potential targets of resveratrol. Then built the TNBC related targets selected by CTD, DisGeNET, and MalaCards databases. Based on the matching results between them, the potential targets for resveratrol against TNBC were obtained. DAVID database was utilized for the enrichment analysis on Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). Then ultilized STRING database and Cytoscape software to build a protein interaction network between targets, and selected the hub genes and core modules by topology. RESULTS A total of 422 potential targets of resveratrol and 1 799 TNBC-related targets were screened, and a total of 130 potential targets of resveratrol against TNBC were obtained after maching, from which 10 hub genes(MAPK1, MAPK3, TP53, SRC, PIK3CA, AKT1, PIK3R1, MAPK8, PTPN11, JAK2) were further confirmed. The KEGG pathway enrichment analysis showed that targets of resveratrol against TNBC were correlated with PI3K-Akt signaling pathway. CONCLUSION Resveratrol may serves as a multi-target, multi-pathway treatment for TNBC, among which the PI3K/Akt pathway may play an important role. The results provide reference for further research on mechanism of resveratrol in the treatment of TNBC.