The Mechanism of Fuzheng Quyu Formula(扶正祛瘀药对)in Treatment of Uterine Leiomyosarcoma Based on Network Pharmacology Study
Objective:To investigate the therapeutic mechanism of Fuzheng Quyu Formula of Huangqi(As-tragalus mongholicus),Dangshen(Codonopsis pilosula),Sanleng(Rhizoma sparganii)and Ezhu(Curcuma zedoaria)on uterine leiomyosarcoma(uLMS)using network pharmacology in order to provide insights for its treatment and research.Methods:Effective components and corresponding targets were retrieved from TCMSP database.The disease-related targets were collected from GeneCards,OMIM,PharmGkb,and DrugBank databases.The inter-section between these two sets of targets was obtained as the putative targets for the Fuzheng Quyu Formula on uLMS.A"compound-target"network was constructed using Cytoscape software.Protein-protein interaction(PPI)network was built with STRING platform and analyzed by Cytoscape software for topology analysis to obtain core genes.GO and KEGG pathway enrichment analyses of the intersecting targets were performed with R language.Molecular docking validation of core genes and active ingredients was conducted using Autodock Vina software.Results of network pharmacology prediction were verified by CCK-8 assay,TUNEL,flow cytometry,and real-time fluorescence quantitative PCR experiments.Results:Network pharmacology screening identified 35 effective components from Fuzheng Quyu Formula,including quercetin,kaempferol,luteolin,etc.These components targeted at 110 disease-relevant targets,which resulted in 12 core genes,including TP53,AKT1,JUN,MYC,etc.GO enrichment analysis covered 2 162 biological processes,42 cellular components,and 152 molecular functions.KEGG enrichment analysis revealed 165 pathways related to uLMS.Fuzheng Quyu Formula may affect cell apoptosis,oxidation reaction,lipopolysaccharide response,etc.,involving lipid metabolism and atherosclerosis signaling pathways such as PI3K-AKT.Core targets and their ligand compounds showed good affinity through molecular docking.In vitro experimental results suggested that Fuzheng Quyu Formula could reduce the viability of uLMS cells,promote their apoptosis,and inhibit the expression of AKT1mRNA and TP53 mRNA in uLMS cells.Conclusion:Fuzheng Quyu Formula can exert an anti-uLMS effect by inhibiting uLMS cell vitality and promoting apoptosis,which is associated with core targets like TP53 and AKT1.
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维普
