目的 基于网络药理学、分子对接及细胞实验探究高良姜素诱导肝细胞癌（hepatocellular carcinoma，HCC）凋亡的作用机制。方法 利用SwissTargetPrediction与PharmMapper数据库预测高良姜素的潜在作用靶点；从GeneCards、TTD与OMIM数据库获取HCC相关靶点。二者取交集后，通过STRING数据库构建蛋白质-相互作用（protein-protein interaction，PPI）网络，并利用DAVID平台对交集靶点进行基因本体（gene ontology，GO）功能与京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。采用AutoDock Vina对高良姜素与核心靶点进行分子对接验证。体外培养人肝癌PLC/PRF/5细胞，通过CCK-8法与流式细胞术分别检测高良姜素对细胞活力与凋亡的影响，并利用Western blotting检测表皮生长因子受体（epidermal growth factor receptor，EGFR）-磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）信号通路及凋亡相关蛋白表达。结果 网络药理学分析共获得高良姜素与HCC的共同作用靶点142个。PPI网络分析显示，EGFR、Akt和半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3，Caspase-3）等蛋白可能是其核心作用靶点。GO与KEGG分析提示，高良姜素可能主要通过调控PI3K/Akt等信号通路影响细胞进程。分子对接结果表明，高良姜素与EGFR等靶点具有较强的结合能力。体外实验证实，高良姜素能显著抑制PLC/PRF/5细胞活力并诱导细胞凋亡（P＜0.01、0.001），显著下调p-EGFR和p-Akt的蛋白表达（P＜0.05），显著上调cleaved Caspase-3和Caspase-9的蛋白表达（P＜0.05、0.01）。结论 高良姜素可能通过抑制EGFR-PI3K/Akt信号通路，诱导HCC细胞凋亡，从而发挥抗HCC的作用。

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.

R285.5

海南省重点研发项目（ZDYF2024SHFZ118）;海南医科大学学术提升计划项目（XSTS2025070）;海南医科大学大学生创新创业训练计划项目（202511810008，X202511810068）