时珍国医国药2026，Vol.37Issue(11)：2029-2038,10.DOI:10.70976/j.1008-0805.SZGYGY-2026-1105
石斛碱通过靶向TOP2A调控氧化应激干预肝癌的机制研究
Study on the mechanism of dendrobine in intervening hepatocellular carcinoma by targeting TOP2A to regulate oxidative stress
摘要
Abstract
Objective To explore the mechanisms by which dendrobine exerts anti-hepatocelllar carcinoma(HCC)effects via oxidative stress regulation using network pharmacology,molecular docking,and experimental validation.Methods Dendrobine targets were pre-dicted on the PubChem and SwissTargetPrediction databases.Oxidative stress-related targets were collected from OMIM and Gen-eCards,and HCC-related data from GEO was used to screen differentially expressed genes.The common targets of dendrobine,HCC,and oxidative stress were identified using the Venny tool.Then,a protein-protein interaction(PPI)network was constructed,and Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were per-formed.Key targets were selected through differential gene expression,receiver operating characteristic(ROC)curve,immunohisto-chemistry(IHC),clinical correlation,and survival prognosis analyses.The binding affinity between core targets and dendrobine was evaluated using molecular docking and molecular dynamics simulation.Finally,the effects of dendrobine on cell proliferation,migra-tion,oxidative stress indicators(e.g.,ROS),and protein expression were assessed via Western blot(WB)and other experiments.Results A total of 26 targets related to dendrobine-regulated oxidative stress were identified.GO and KEGG analyses suggested that dendrobine may work by regulating cell proliferation and signal transduction.The top five PPI targets were selected for further analysis,and the results showed that EZH2,CCNA2,and TOP2A were key targets with significant roles.Molecular docking results showed that TOP2A had the lowest binding energy with dendrobine,indicating the strongest binding affinity,and molecular dynamics simulation con-firmed the stable binding between them.Experimental results showed that dendrobine could suppress HepG2 cell proliferation and migration,reduce intracellular ROS levels,and downregulate TOP2A expression.Conclusion Dendrobine intervenes in HCC by target-ing TOP2A to regulate oxidative stress.关键词
石斛碱/肝癌/氧化应激/TOP2AKey words
Dendrobine/Hepatocellular carcinoma/Oxidative stress/TOP2A分类
医药卫生引用本文复制引用
李军,胡飞,郭云辉,楼迪栋..石斛碱通过靶向TOP2A调控氧化应激干预肝癌的机制研究[J].时珍国医国药,2026,37(11):2029-2038,10.基金项目
国家级大学生创新创业训练计划项目(2024106620634) （2024106620634）
贵州中医药大学大学生创新创业训练计划项目(贵中医大创合字[2024]62号) （贵中医大创合字[2024]62号）
贵州省科技计划项目(黔科合基础-ZK[2024]一般382) （黔科合基础-ZK[2024]一般382）
