基于网络药理学探究逍遥散治疗乳腺癌的潜在机制

目的： 利用网络药理学探究逍遥散治疗乳腺癌（BC）的潜在机制。方法： 从中药系统药理学分析平台（TCMSP）收集组方药物的活性成分及靶点，与Genecards网站收集的乳腺癌靶点取交集后，筛选出逍遥散治疗乳腺癌的潜在靶点，进而绘制中药-活性成分-靶点网络图并分析其核心成分，构建靶蛋白互作网络并分析其核心靶点，并进行基因本体（GO）分子功能和京都基因与基因组百科全书（KEGG）通路富集分析，最后通过分子对接探究核心成分与核心靶点的相互作用。结果： 逍遥散治疗乳腺癌的核心成分为槲皮素、木犀草素和山奈酚，核心靶点为AKT1、IL-6和VEGFA，分子对接表明核心成分与AKT1有较好的结合作用。相关通路机制涉及细胞增殖和凋亡、免疫功能、血管生成、骨质破坏和药物耐药，其中PI3K-Akt信号通路很可能是逍遥散干预的通路。结论： 逍遥散治疗乳腺癌具有多成分、多靶点、多通路综合作用机制，这可为今后阐明逍遥散治疗乳腺癌的具体机制提供参考。

Potential mechanism of Xiaoyao San for breast cancer based on network pharmacology

OBJECTIVE To explore the potential mechanism of Xiaoyao San for breast cancer (BC) by the method of network pharmacology.METHODS Active ingredients of Xiaoyao San with their corresponding targets were retrieved from the TCMSP and combined with BC-related genes collected from the Gene cards website so that overlapping targets were kept, which were regarded as the potential targets of Xiaoyao San for BC. A herb-active ingredient-target network was construct and analyzed for key ingredients. A protein-protein interaction network was built and studied for key targets. Furthermore, GO molecular function and KEGG pathway enrichment analysis were carried out. Finally, relations between key ingredients and key genes were evaluated by the method of molecular docking.RESULTS Key ingredients of Xiaoyao San for BC may be Quercetin,Luteolin and Kaempferol while key therapeutic targets may be protein kinase B(PKB or AKT1),interleukin-6(IL-6) and vascular endothelial growth factor A(VEGFA). Molecular docking showed that the core components had a good binding effect with AKT1. The related pathway mechanisms involve cell proliferation and apoptosis, immune function, angiogenesis, bone destruction, and drug resistance, of which the PI3K-Akt signaling pathway is likely to be the pathway intervened by Xiaoyao San.CONCLUSION Xiaoyao San has a multi-component, multi-target and multi-pathway comprehensive mechanism of action in the treatment of breast cancer, which provides a reference for elucidating the specific mechanism of Xiaoyao San in the treatment of breast cancer in the future.