Objective To explore the mechanism of galangin-induced apoptosis in hepatocellular carcinoma (HCC) based on network pharmacology, molecular docking and cell experiment. Methods Potential targets of galangin were predicted using SwissTargetPrediction and PharmMapper databases, HCC-related targets were collected from GeneCards, TTD and OMIM databases. The intersection of these targets was used to construct a protein-protein interaction (PPI) network via STRING database, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of intersected targets using DAVID platform. Molecular docking of galangin with core targets was validated using AutoDock Vina. Human hepatocellular carcinoma PLC/PRF/5 cells were cultured in vitro, and the effects of galangin on cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry. Western blotting was used to detect the expressions of epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and apoptosis-related proteins. Results Network pharmacology analysis identified 142 common targets between galangin and HCC. PPI network analysis revealed that proteins such as EGFR, Akt and cystein-asparate protease-3 (Caspase-3) may serve as core targets. GO and KEGG analyses suggested that galangin primarily influenced cellular processes by regulating PI3K/Akt signaling pathway. Molecular docking results indicated galangin had strong binding affinity with targets such as EGFR. In vitro experiments confirmed that galangin significantly inhibited PLC/PRF/5 cells viability and induced apoptosis (P < 0.01, 0.001), significantly down-regulated p-EGFR and p-Akt protein expressions (P < 0.05), and significantly up-regulated cleaved Caspase-3 and Caspase-9 protein expressions (P < 0.05, 0.01). Conclusion Galangin may exert its anti-HCC effects by inhibiting EGFR-PI3K/Akt signaling pathway and inducing apoptosis in HCC cells.

galangin  /  hepatocellular carcinoma  /  network pharmacology  /  apoptosis  /  EGFR-PI3K/Akt signaling pathway