参苓白术散治疗结直肠癌的网络药理学机制及分子靶点探讨

Network pharmacological mechanism and molecular targets of Shenling Baizhu Powder in treating colorectal cancer

为探究参苓白术散(Shenling Baizhu powder,SLBZP)治疗结直肠癌的作用机制。运用网络药理学的方法,通过TCMSP数据库收集、筛选SLBZP的活性成分并获得作用靶点,GEO数据库筛选获得CRC患者与健康个体之间的差异表达基因作为CRC的相关靶点。借助Cytoscape软件构建药物成分、疾病靶点网络,Bisogenet构建蛋白质相互作用(PPI)网络,以识别SLBZP作用于CRC的候选靶点。通过基因本体(GO)功能富集京都基因与基因组百科全书(KEGG)通路富集分析核心基因的生物学功能及通路富集情况。Cytoscape软件构建了靶点-途径网络,根据Degree筛选关键靶基因。通过分析得到SLBZP治疗CRC的核心靶点165个,发现核心靶点功能注释与转录因子的活性、蛋白质稳定性调节、泛素蛋白连接酶结合等有关。PI3K-Akt信号通路,PD-L1/PD-1途径,病毒致癌等二十个途径均得到显著的富集。AKT1、TP53、PIK3R1为核心基因,MAPK3、NFKB1、CCND1、MAPK1、RELA、CDKN1A、MYC、STAT3、MDM2、JUN、RB1等是SLBZP网络途径中治疗CRC的关键基因。综上SLBZP对CRC的治疗作用可能与特定的生物学过程及相关途径调节炎性反应、优化肠道菌群结构发挥治疗作用。通过网络药理学分析评估,SLBZP复杂的作用机理及作用靶标得到了进一步的揭示,对CRC治疗意义重大。

To explore the mechanism of Shenling Baizhu Powder(SLBZP)in the treatment of colorectal cancer.Using the method of network pharmacology,the active ingredients of SLBZP were collected and screened through the TCMSP database and the targets were obtained.The GEO database was screened to obtain differentially expressed genes between CRC patients and healthy individuals as the relevant targets of CRC.Cytoscape software was used to construct a network of drug components and disease targets.Bisogenet was used to construct a protein interaction(PPI)network to identify candidate targets for SLBZP acting on CRC.Through gene ontology(GO)function enrichment,Kyoto Encyclopedia of Genes and Genomics(KEGG)pathway enrichment analysis was used for biological functions and pathway enrichment of core genes.Cytoscape software was used to constructs a target-pathway network and screen key target genes according to degree.Through analysis,165 core targets of SLBZP for the treatment of CRC were found,and it was found that the functional annotation of core targets was related to transcription factor activity,protein stability regulation,and ubiquitin protein ligase binding.Twenty pathways including PI3K-Akt signaling pathway,PD-L1/PD-1 pathway,and viral carcinogenesis are all significantly enriched.AKT1,TP53,PIK3R1 are the core genes,and MAPK3,NFKB1,CCND1,MAPK1,RELA,CDKN1A,MYC,STAT3,MDM2,JUN,RB1,etc.are the key genes for the treatment of CRC in the SLBZP network pathway.In summary,the therapeutic effect of SLBZP on CRC may be related to specific biological processes and related pathways to regulate inflammatory responses and optimize the structure of intestinal flora to play a therapeutic role.Through network pharmacological analysis and evaluation,the complex mechanism and targets of SLBZP have been further revealed,which is of great significance to the treatment of CRC.