多技术整合探究芪枣保心方治疗乳腺癌的作用机制OA

OBJECTIVE:To investigate the active components,potential targets,and possible mechanisms of Qizao Baoxin formula in the treatment of breast cancer by integrating network pharmacology,molecular docking,and molecular dynamics simulation.METHODS:The chemical constituents and corresponding protein targets of Qizao Baoxin formula were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform.Breast cancer-related targets were obtained from the GeneCards,OMIM,and TTD databases,and the intersecting targets between the two sets were identified.These intersecting targets were imported into the STRING database to construct a protein-protein interaction(PPI)network,and an active compound-target network was established by using Cytoscape 3.10.3.Key targets and core compounds were screened through topological analysis.Gene ontology functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersecting targets via the Metascape platform.Molecular docking was conducted by using AutoDock 1.5.7,followed by molecular dynamics simulation to evaluate the stability of the optimal docking complexes.RESULTS:A total of 158 intersecting targets were identified,among which tumor protein p53,protein kinase B1,signal transducer and activator of transcription 3,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were the key targets of Qizao Baoxin formula in the treatment of breast cancer.KEGG enrichment analysis indicated that the mechanism of Qizao Baoxin formula in the treatment of breast cancer was related to multiple signaling pathways such as TNF-α,advanced glycation end products(AGE)-AGE receptors,and IL-17.Molecular docking combined with molecular dynamics simulation revealed that luteolin formed stable complexes with six key targets.CONCLUSIONS:The active compounds of Qizao Baoxin formula may act on breast cancer-related targets through multiple pathways in a synergistic manner,providing a new therapeutic idea for the study of the multi-component and multi-target mechanism of action mediated by Qizao Baoxin formula against breast cancer.