Molecular mechanism of luteolin for inhibiting esophageal squamous cell carcinoma based on network pharmacology and in vitro studies

doi:10.19803/j.1672-8629.20220744

Abstract

Abstract: Objective To investigate the molecular mechanism by which luteolin inhibits esophageal squamous cell carcinoma (ESCC) based on network pharmacology and in vitro studies. Methods The common targets of luteolin and ESCC were identified by constructing Venn diagrams of active ingredients and diseases. The common targets were visualized via the String database before a protein-protein interaction network (PPI) was established. The Hub genes were screened using the plug-in of Cytoscape 3.9.1. Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were performed using the R programming language. The inhibitory effect of luteolin on ESCC cell lines (TE-13 and KYSE-510) was observed in vitro, and the binding activity of luteolin and Hub genes was verified by molecular docking. Results A total of 69 common targets of luteolin and ESCC were collected, and Hub target genes represented by AKT1, ESR1 and SRC were screened. The targets involved not only such biological functions as cellular oxidative stress and protein modification, but such signaling pathways as reactive oxygen species, inflammation, and extracellular matrix. The PI3K-Akt signaling was selected to verify the rationality of the results of the network pharmacology analysis. In vitro studies showed that luteolin inhibited the ability of TE-13 and KYSE-510 cells to proliferate, migrate, and invade, and reduced the expressions of phosphorylated proteins in the FAK-SRC-PI3K-Akt pathway. In addition, the results of molecular docking showed that luteolin showed good affinity for FAK, SRC and Akt. Conclusion The inhibition of ESCC by luteolin is characterized by multiple targets and multiple pathways, which may be related to the inhibition of the FAK-SRC-PI3K-Akt pathway.

Key words: luteolin, esophageal squamous cell carcinoma, network pharmacology, molecular docking, signaling pathway, mechanism of action

CLC Number:

R994.11
R285

YANG Zhenzhen, CHANG Cheng, GAO Na, ZHANG Xiaolin, SONG Yinsen, LIU Ying, FAN Tianli. Molecular mechanism of luteolin for inhibiting esophageal squamous cell carcinoma based on network pharmacology and in vitro studies[J]. Chinese Journal of Pharmacovigilance, 2023, 20(9): 992-1001.

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