基于网络药理学和免疫浸润探讨路路通-桂枝作用于乳腺癌免疫调节机制研究

To Study the Immune Regulation Mechanism of Liquidambaris Fructus-Cinnamomi Ramulus on Breast Cancer Based on Network Pharmacology and Immune Infiltration

目的利用网络药理学和免疫浸润探讨路路通-桂枝作用于乳腺癌(Breast cancer,BC)免疫调节的作用机制。方法分别利用TCMSP、GeneCards等数据库获得路路通-桂枝的有效成分及靶点、BC以及免疫调节的相关基因。通过Cytoscape软件构建药物-成分-靶点网络图,同时使用STING网站构建蛋白相互作用信息图(PPI)。使用DA VID数据库对交集基因进行GO功能富集和KEGG通路富集分析,并通过分子对接预测活性成分与关键靶点的结合活性,使用GEPIA、TIMER数据库对核心靶标进行表达和免疫浸润分析。结果共获得11个活性成分,药物-疾病共同靶蛋白23个。PPI显示,前4位关键靶点为JUN、ESR1、CASP3、HSP90AA1。突出活性成分为beta-sitosterol。KEGG富集结果表明,p53信号通路是其关键的信号通路。分子对接结果表明关键成分与关键靶点具有良好的结合活性。这些结果在mRNA表达水平、生存曲线和免疫浸润方面得到了进一步验证。结论路路通-桂枝通过多成分、多靶点、多途径的方式发挥免疫调节治疗BC的作用,从而为其临床应用及相关机制的研究提供了理论依据。

OBJECTIVE To explore the mechanism of Liquidambaris Fructus and Cinnamomi ramulus effect on immune regulation of breast cancer(BC)by network pharmacology and immune infiltration.METHODS The active components,target,BC,and immune regulation genes were obtained by using TCMSP and GeneCards databases.Protein-Protein Interaction Networks(PPI)were constructed using STING website.In addition,Cytoscape software was used for analysis,KEGG and GO functional enrichment analysis were carried out,and the binding activity of active ingredients and key targets was predicted by molecular docking.The core targets were further analyzed by GEPIA and TIMER databases.RESULTS A total of 11 active ingredients and 23 common target proteins of drug and disease were obtained.PPI showed that the key targets were JUN,ESR1,CASP3,HSP90AA1,etc.The active ingredient was beta-sitosterol.KEGG enrichment results showed that p53 signaling pathway was the key signaling pathway.The results of molecular docking showed that the key components had a good binding activity with the key targets.These results were further validated in terms of mRNA expression levels,survival analysis,and immune infiltration.CONCLUSION Liquidambaris Fructus-Cinnamomi Ramulus plays the role of immune reg ulation in the treatment of BC through multi-component,multi-target,and multi-pathway,which provides a theoretical basis for its clinical application and related mechanism research.