Molecular mechanism of Eriobotryae Folium against triple-negative breast cancer based on network phar-macology and experimentation
OBJECTIVE To explore the mechanism of Eriobotryae Folium on triple-negative breast cancer based on network pharmacology and experimentation.METHODS The TCMSP database was used to obtain the main chemical constituents and targets of Eriobotryae.GeneCards,OMIM,and DisGeNET database were used to obtain the relevant targets for triple-negative breast cancer.Protein-protein interaction analysis was performed by String platform.Metascape database was used to analyze the biological processes and pathways involved in the potential targets of Eriobotryae,and molecular docking validation was performed by CB-Dock.The influence of potential pharmacological components of Eriobotryae on the proliferative activity of 4T1 cells was examined by MTT assay and plate clone formation assay.The related protein expression levels were detected by Western Blot.RESULTS Eighteen potential active components and 147 potential targets of Eriobotryae against triple-negative breast cancer were identified.Oleanolic acid(OA),(-)-epigallocatechin gallate(EGCG),and other components of Eriobotryae showed a strong affinity with targets such as TP53 and AKT1.OA and EGCG inhibited 4T1 proliferation,reducing p-AKT,p-mTOR pro-tein expression and upregulating the cell cycle regulator p27 expression level in a time-and dose-dependent manner.CONCLUSION OA and EGCG in Eriobotryae suppress the invasion and replication of triple-negative breast cancer cells by regulating the PI3K-AKT signaling pathway and upregulating the cell cycle regulator p27 to achieve anti-proliferation of breast can-cer cells.
Eriobotryae Foliumtriple-negative breast cancernetwork pharmacologymolecular mechanism