基于生物信息学方法探讨白花蛇舌草-半枝莲抗乳腺癌的分子机制

MOLECULAR MECHANISM OF HEDYOTIS DIFFUSA WILLD.-SCUTELLARIA BARBATA AGAINST BREAST CANCER BASED ON BIOINFORMATICS METHOD

目的通过生物信息学及网络药理学方法,探讨白花蛇舌草(HDW)-半枝莲(SB)治疗乳腺癌(BC)的分子机制。方法通过中药系统药理数据库(TCMSP)筛选HDW-SB共同有效成分及有效成分的潜在靶点基因,使用基因表达综合数据库(GEO)中GSE45827芯片筛选出BC组织和癌旁正常组织差异表达基因(DEGs),建立HDW-SB共同有效成分所调控的BC靶点的蛋白质-蛋白质相互作用(PPI)网络,经拓扑分析和预后价值分析筛选出BC关键靶点。最后,通过对BC关键靶点与HDW-SB共同有效成分进行分子对接,筛选出HDW-SB核心有效成分。结果共鉴定出25种HDW-SB共同有效成分,并筛选出544个BC DEGs,分别构建BC DEGs和HDW-SB共同有效成分所调控的BC靶点的PPI网络;拓扑分析和预后价值分析确定BC的关键靶点为HSPB1、CCNA2和NQO1,分子对接分析显示,HDW-SB治疗BC的核心有效成分为quercetin、rhamnoside和luteolin。结论HWD-SB可能是通过干预HSPB1、CCNA2和NQO1达到治疗BC的作用。

Objective To investigate the molecular mechanism of Hedyotis diffusa Willd.(HDW)and Scutellaria barbata(SB)in the treatment of breast cancer(BC)based on bioinformatics and network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen out the common effective constituents of HDW and SB and their potential target genes,and Gene Expression Omnibus(GEO)database was used screen out differentially expressed genes(DEGs)between BC tissue and adjacent tissue.A protein-protein interaction(PPI)network was established for the BC targets regulated by the common effective constituents of HDW and SB,and then topological analysis and prognostic value analysis were performed to screen out the key targets of BC.Finally,molecular docking was performed for the key targets of BC and the common effective constituents of HDW and SB to screen out the core effective constituents of HDW-SB.Results A total of 25 common effective constituents of HDW-SB were identified,and 544 DEGs associated with BC were screened out.PPI networks were established for BC DEGs and the BC targets regulated by the common effective constituents of HDW-SB,and topological ana-lysis and prognostic value analysis determined that HSPB1,CCNA2,and NQO1 were the key targets of BC.Meanwhile,molecular docking showed that quercetin,rhamnoside,and luteolin were the core effective constituents of HDW-SB.Conclusion HWD-SB may exert a therapeutic effect on BC by regulating HSPB1,CCNA2,and NQO1.