安徽中医药大学学报2025，Vol.44Issue(3)：65-74,10.DOI:10.3969/j.issn.2095-7246.2025.03.015
基于网络药理学及动物实验探讨藤黄总酸抗肝细胞癌的作用机制
Mechanism of Action of Gambogic General Acids in Treatment of Hepatocellular Carcinoma:A Study Based on Network Pharmacology and Animal Experiments
摘要
Abstract
Objective To investigate the potential antitumor targets and mechanism of action of gambogic general acids(GGAs)in the treatment of hepatocellular carcinoma(HCC).Methods The method of network pharmacology was used to obtain the potential active components and targets of GGAs,and molecular docking was used to simulate the docking pattern between core targets and components.H22 hepatoma cells were used to establish a mouse model of subcutaneous graft tumor,and then the mice randomly divided into control group(normal saline),diammine dichloroplatinum-Ⅱ(DDP)group(2 mg/kg),low-dose GGAs group(20 mg/kg),and high-dose GGAs group(40 mg/kg).The impact of GGAs on tumor growth was observed.Im-munohistochemistry was used to measure the positive expression of phosphatidylinositol-3-kinase(PI3K),protein kinase B(AKT),and phosphorylated AKT(p-AKT),and Western blot and RT-qPCR were used to measure the protein and mRNA expression levels of PI3K,AKT,p-AKT,Bax,Bcl-2,and cleaved caspase-3 in tumor tissue.Results A total of 16 main ac-tive components and 4 key targets were obtained for GGAs in the treatment of HCC based on network pharmacology.The stud-y of mechanisms showed that the potential mechanism of GGAs in tumor treatment involved the regulation of cancer-related pathways,the PI3K/AKT signaling pathway,and cell apoptosis pathways,and the key active component neogambogic acid had strong binding affinity with the core target AKT1.The results of animal experiments showed that GGAs significantly reduced the expression of Bcl-2 protein in tumor tissue,increased the protein expression of Bax and cleaved caspase-3,and inhibited the over-activation of the PI3K/AKT signaling pathway,thereby exerting an antitumor effect.Conclusion The key target AKT1 obtained by network pharmacology and animal experiments show that GGAs may exert a therapeutic effect on HCC by regula-ting the PI3K/AKT signaling pathway.关键词
藤黄总酸/肝细胞癌/PI3K/AKT信号通路/网络药理学Key words
Gambogic general acids/Hepatocellular carcinoma/PI3K/AKT signaling pathway/Network pharmacology分类
临床医学引用本文复制引用
杨奇奇,姚媛,庞梦迪,殷富生,何俊,吴金延,陈卫东,王妍妍..基于网络药理学及动物实验探讨藤黄总酸抗肝细胞癌的作用机制[J].安徽中医药大学学报,2025,44(3):65-74,10.基金项目
国家自然科学基金项目(82073923) （82073923）
国家自然科学基金青年项目(82204748) （82204748）
