[1]李禄阳,柳成刚.基于网络药理学和体外实验模型探讨淫羊藿素对肝细胞癌的抑制作用及潜在机制[J].陕西医学杂志,2025,54(12):1587-1595.[doi:DOI:10.3969/j.issn.1000-7377.2025.12.001]
　LI Luyang,LIU Chenggang.Inhibitory effect and potential mechanism of icaritin on hepatocellular carcinoma were explored based on network pharmacology and in vitro experimental models[J].,2025,54(12):1587-1595.[doi:DOI:10.3969/j.issn.1000-7377.2025.12.001]
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基于网络药理学和体外实验模型探讨淫羊藿素对肝细胞癌的抑制作用及潜在机制

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年12期
页码:
1587-1595
栏目:
基础研究
出版日期:
2025-12-05

文章信息/Info

Title:
Inhibitory effect and potential mechanism of icaritin on hepatocellular carcinoma were explored based on network pharmacology and in vitro experimental models
作者:
李禄阳; 柳成刚
（黑龙江中医药大学基础医学院，黑龙江 哈尔滨 150040）
Author(s):
LI Luyang; LIU Chenggang
(Basic Medical College,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China)
关键词:
肝细胞癌; 淫羊藿素; 网络药理学; 磷脂酰肌醇3-激酶; 蛋白激酶B; 信号通路
Keywords:
Hepatocellular carcinoma; Icaritin; Network pharmacology; Phosphatidylinositol 3-kinase; Protein kinase B; Signaling pathway
分类号:
R 735.7
DOI:
DOI:10.3969/j.issn.1000-7377.2025.12.001
文献标志码:
A
摘要:
目的：基于网络药理学与体外实验探讨淫羊藿素（ICA）对肝细胞癌（HCC）的抑制作用及潜在机制。方法：通过文献查阅及药物、疾病相关数据库获取ICA与HCC相关靶点，利用韦恩图经可视化与分析获取两者交集基因，构建蛋白质相互作用网络筛选核心靶点并分析基因富集和生物过程。在网络药理学分析的基础上，采用CCK-8法、划痕愈合实验确定ICA对HepG2细胞增殖及迁移能力的影响，采用流式细胞术分析ICA对细胞凋亡的影响，采用蛋白质印记法（Western blot）检测凋亡相关蛋白和磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）通路相关蛋白的表达变化。结果：共筛选得到113个ICA相关靶点和8547个HCC相关靶点，经交叉得到77个ICA作用于HCC的可能靶点。蛋白质-蛋白质互作网络（PPI）分析共鉴定出10个核心基因。富集分析结果显示，ICA通过影响多种通路发挥抗HCC作用，其中PI3K/AKT通路可能是主要的调控途径。CCK-8和划痕愈合实验结果显示，ICA以浓度依赖性方式抑制HepG2细胞的增殖和迁移（均P<0.05）。流式细胞术结果显示，不同浓度ICA能够显著诱导HepG2细胞凋亡（均P<0.05）。Western blot实验结果显示，ICA处理导致HepG2细胞中磷酸化PI3K（p-PI3K）、磷酸化AKT（p-AKT）、B淋巴细胞瘤-2蛋白（Bcl-2）和酶原型胱天蛋白酶3（Pro-caspase-3）蛋白表达水平显著降低，而Bcl-2相关X蛋白（Bax）和剪切型胱天蛋白酶3（Cleaved-caspase-3）表达显著增加（均P<0.05）；在加入PI3K激活剂740Y-P后，与单独ICA干扰比较，ICA联合740Y-P处理组p-PI3K、p-AKT和凋亡相关蛋白水平被有效逆转（均P<0.05）。结论：ICA能有效抑制HCC细胞增殖、迁移并诱导细胞凋亡，这可能与其抑制PI3K/AKT通路的激活有关。
Abstract:
Objective:To explore the inhibitory effect of icaritin (ICA) on hepatocellular carcinoma (HCC) and its potential mechanism based on network pharmacology and in vitro experiments.Methods：ICA and HCC-related targets were identified via literature review and drug and disease-related databases.Venn diagrams facilitated the visualization and analysis of intersecting genes between the two.A protein-protein interaction network was constructed to identify core targets and analyze gene enrichment and biological processes.Based on network pharmacology analysis,the CCK-8 assay was employed to evaluate the effect of ICA on HepG2 cell proliferation.The scratch healing assay assessed ICA's impact on cell migration capacity.Flow cytometry was utilized to examine the effect of ICA on cell apoptosis.The expression changes of apoptosis-related proteins and proteins related to PI3K/AKT pathway were detected by Western blot.Results:A comprehensive screening identified 113 targets associated with ICA and 8547 targets related to HCC,resulting in the identification of 77 potential targets for ICA's action on HCC through cross-referencing.Protein-protein interaction (PPI) network analysis revealed 10 core genes.Enrichment analysis indicated that ICA exerts its anti-HCC effects by modulating multiple signaling pathways,with the PI3K/AKT pathway potentially serving as the primary regulatory pathway.Results from CCK-8 and scratch assays demonstrated that ICA inhibited the proliferation and migration of HepG2 cells in a concentration-dependent manner (all P<0.05).Flow cytometry analysis revealed that different concentrations of ICA significantly induced apoptosis in HepG2 cells (all P<0.05).Western blot analysis showed that ICA treatment significantly decreased the protein expression levels of p-PI3K,p-AKT,Bcl-2,and Pro-caspase-3 in HepG2 cells,while significantly increasing the expression of Bax and Cleaved-caspase-3 (all P<0.05);upon combination with the PI3K activator 740Y-P,the ICA-740Y-P treatment group demonstrated a significant reversal of the decreased levels of p-PI3K,p-AKT,and apoptosis-related proteins,in comparison to treatment with ICA alone (all P<0.05).Conclusion:ICA can effectively inhibit the proliferation and migration of HCC cells and induce cell apoptosis.This may be related to its ability to inhibit the activation of the PI3K/AKT pathway.

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备注/Memo

备注/Memo:
国家中医药管理局龙江医学流派传承工作室建设项目（LPGZS2012-14）
更新日期/Last Update: 2025-12-05