Molecular mechanism of quercetin intervention for Breast cancer based on network pharmacology and cell experiment
Objective To predict the potential molecular mechanisms of quercetin in the intervention of breast cancer based on network pharmacology and molecular docking,and to observe the effects of quercetin on proliferation,migration,and epithelial-mesenchymal transition(EMT)of breast cancer cells and to verify the possible signaling pathways.Methods Swiss Target Prediction and PubChem database were used to screen potential targets of quercetin.The targets of breast cancer were obtained from OMIM,TTD,CTDbase and DisGeNET database.The common targets of both were obtained after taking the intersection,and Protein-protein interaction(PPI)network was constructed with String database and topological analysis was carried out via Cytoscape software to screen core targets.GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database.AutoDock Vina software was used for molecular docking,using related proteins on key signaling pathways as receptor and quercetin as ligand.In vitro model of breast cancer was established by MDA-MB-468 cells,and cell proliferation and migration invasion were observed by CCK-8 method,cell scratching and Transwell assay.Western blot was used to detect the expression levels of proliferation,apoptosis,EMT-related proteins,and phosphorylation of related proteins on key signaling pathways.Results A total of 103 quercetin related tar-gets and 2526 breast cancer related targets were excavated,with a total of 53 common targets.PPI network included 12 core targets.There were 563 GO functional items and 109 KEGG signaling pathways were en-riched.The molecular docking results showed that quercetin had a strong binding activity to the related pro-teins.In vitro experiments showed that quercetin could inhibit the proliferation,migration invasion and EMT of breast cancer cells.Western blot showed that quercetin down-regulated the relative expression levels of PCNA,Bcl-2,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR(P<0.01,P<0.05),while the relative expression level of Bax was up-regulated(P<0.01,P<0.05).Conclusion Quercetin has multiple ingredi-ents and targets in the intervention of breast cancer.It may be related to the inhibition of PI3K-AKT-mTOR signaling pathway and induction of apoptosis,which provides a scientific basis for the further investigation and clinical application of quercetin.
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