葛根素治疗肝细胞癌的机制研究

Mechanism of Puerarin in the Treatment of Hepatocellular Carcinoma

目的:基于网络药理学、生物信息学及分子对接技术探讨葛根素治疗肝细胞癌(HCC)的作用机制。方法:从TCMSP等数据库中获取葛根素作用靶点;美国国家生物技术信息中心(NCBI)-基因表达综合数据库(GEO)中获取HCC数据集;HDDb数据库中获取细胞自噬靶点。三者靶点取交集并构建PPI网络,交集靶点进行分子对接、蛋白表达图谱、临床相关性、生存分析、差异表达、ROC曲线和KEGG通路富集分析。结果:最终获得5个交集靶点,分子对接显示有3个蛋白(RHEB、FAS、SERPINA1)能与葛根素高度结合。蛋白表达图谱提示在HCC中RHEB呈高表达,FAS、SERPINA1呈低表达。临床相关性分析、生存分析、差异表达分析和ROC曲线均支持RHEB在葛根素通过作用于细胞自噬治疗HCC。KEGG通路富集显示RHEB参与mTOR-自噬通路。结论:葛根素可能通过作用于自噬相关基因RHEB,从而起到治疗HCC的作用。

Objective:To explore the mechanism of puerarin in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology,bioinformatics and molecular docking techniques.Methods:The target of puerarin was obtained from TCMSP and other databases.HCC data sets were obtained from the National Center of Biotechnology Information(NCBI)-Integrated Gene Expression Database(GEO).Autophagy targets were obtained from HDDb database.The targets of the three were intersected and PPI networks were constructed.The intersection targets were analyzed for molecular docking,protein expression profile,clinical correlation,survival analysis,differential expression,ROC curve and KEGG pathway enrichment analysis.Results:A total of 5 intersection targets were obtained,and molecular docking showed that 3 proteins(RHEB,FAS,SERPINA1)were highly binding to puerarin.The protein expression profile indicated that RHEB was highly expressed in HCC,while FAS and SERPINA1 were low expressed.Clinical correlation analysis,survival analysis,differential expression analysis and ROC curve all supported that RHEB of puerarin treated HCC by acting on autophagy.KEGG pathway enrichment showed that RHEB was involved in the mTOR-autophagy pathway.Conclusion:Puerarin may play a role in the treatment of HCC by acting on RHEB,a gene associated with autophagy.