南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (6): 805-814.doi: 10.12122/j.issn.1673-4254.2022.06.03

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益气解毒方治疗原发性肝癌的作用机制：基于网络药理学及分子对接方法

徐 朦，张 鹏，张国梁   

  1. 安徽中医药大学研究生院，第一附属医院，安徽 合肥 230038；安徽医科大学第一附属医院普外科，安徽 合肥 230022
  • 出版日期:2022-06-20 发布日期:2022-06-28

Exploration of the therapeutic mechanism of Yiqi Jiedu recipe for treatment of primary liver cancer based on network pharmacology and molecular docking

XU Meng, ZHANG Peng, ZHANG Guoliang   

  1. Graduate School, Department of Infection, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230038,China; Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
  • Online:2022-06-20 Published:2022-06-28

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摘要： 目的 通过网络药理学及分子对接探究益气解毒方的有效成分及其作用于原发性肝癌的主要生物过程及信号通路，阐明益气解毒方治疗原发性肝癌的作用机制。方法 通过TCMSP、Uniport、Genecards、String等数据库，以及Cytoscape3.8.2软件得出药物、疾病最终靶点基因；通过David数据库对药物-疾病共有基因做GO、KEGG富集分析；通过Pubcham、RCSB、Autoduck将药物有效成分与最终核心基因进行分子对接；通过细胞活力检测、Western blot、实时荧光定量PCR实验研究不同浓度的益气解毒方对于核心基因DHX9、HNRNPK、NCL、PABPC1表达的影响。结果 筛选得出8个最终核心基因：DDX5、HNRNPK、PABPC1、DHX9、RPS3A、RPS3、RPL13、NCL。GO分析显示：主要生物过程为Ephrin receptor signaling pathway、Movement of cell or subcellular component、Blood microparticle、Focal adhesion、Iron ion binding；KEGG分析显示：Ras信号通路的基因数最多。分子对接结果显示药物有效成分与最终核心基因均可以在自然条件下进行对接，其中PABPC1与Stigmasterol结合能最高。Western blot、实时荧光定量PCR实验结果显示，当含药血清浓度逐渐增大时，细胞活力逐渐受到抑制（P<0.01），HepG2中蛋白相对表达量逐渐降低（P<0.05）；HepG2中蛋白的mRNA相对表达量逐渐增高（P<0.05），HepG2+10%含药血清培育48 h对HepG2 中 DHX9、HNRNPK、NCL、PABPC1 表达影响最明显（P<0.05）。结论 益气解毒方通过多种有效成分与 DHX9、HNRNPK、NCL、PABPC1的结合，调节原发性肝癌的的病毒表达，从而治疗原发性肝癌。

关键词: 益气解毒方；原发性肝癌；网络药理学；分子对接

Abstract: Objective To explore the effective components of Yiqi Jiedu recipe and the main biological processes and signal pathways involved in the therapeutic mechanism of the recipe in treatment of primary liver cancer through network pharmacology and molecular docking approaches. Methods TCMSP, Uniport, Genecards and String databases were searched to obtain the target genes of drugs and disease using Cytoscape 3.8.2 software. GO and KEGG enrichment analyses were performed to identify the common genes in the target genes of the drugs and disease. Using Pubcham, RCSB and Autoduck, the effective components of the drugs were connected with the final core genes. The effects of different concentrations of Yiqi Jiedu recipe on the expressions of the core genes DHX9, HNRNPK, NCL and PABPC1 in HepG2 cells were analyzed with Western blotting and real- time fluorescence quantitative PCR. Results We finally identified 8 core genes from the drug and disease targets, including DDX5, HNRNPK, PABPC1, DHX9, RPS3A, RPS3, RPL13, and NCL. GO analysis showed that these core genes were involved mainly in the biological processes of adrenaline receptor signal communication, movement of cellular or subcellular components, blood particles, adhesion class and iron ion binding. KEGG analysis showed that the Ras signaling pathway had the greatest gene enrichment. The results of molecular docking suggested that the effective components of the recipe were capable of docking with the core genes under natural conditions, and PABPC1 and stigmasterol had the highest binding energy. In HepG2 cells, treatment with 10% medicated serum for 48 h had the strongest effect on the expression of DHX9, HNRNPK, NCL and PABPC1 (P<0.05). Conclusion Yiqi Jiedu recipe is capable of regulating viral expression of primary liver cancer multiple effective components that bind to DHX9, HNRNPK, NCL and PABPC1.

Key words: Yiqi Jiedu recipe; primary liver cancer; network pharmacology; molecular docking