基于网络药理学探讨香叶醇抑制结肠癌的作用机制研究

Study on the mechanism of geraniol inhibiting colon cancer based on network pharmacology

目的基于网络药理学和分子对接技术研究香叶醇抑制结肠癌的作用机制。方法通过PubChem获得香叶醇的2D、3D结构图,通过Swiss Target Prediction平台获得香叶醇单体对应的靶点信息,通过GeneCards数据库、OMIM数据库、TTD数据库获得与结肠癌相关的疾病靶点,并通过基因芯片数据平台(GEO)数据库,分析基因芯片,得到结肠癌的差异基因,通过Cytoscape3.8.2软件构建网络分析图,利用Metascape对交集基因进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析,通过分子对接结合文献验证。结果香叶醇对应的靶点基因有111个,GEO数据库与公共数据库交集基因396个,香叶醇与结肠癌交集基因18个;其中表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶8(MAPK8)、丝裂原活化蛋白激酶激酶1(MAP2K1)、MAPK14、雄激素受体(AR)、酪氨酸蛋白激酶JAK2、孕酮受体(PGR)、G2/有丝分裂特异性细胞周期蛋白B1(CCNB1)为关键靶点,主要涉及Janus激酶/信号转导和转录激活因子(JAK/STAT)、丝裂原活化蛋白激酶(MAPK)等癌症相关信号通路及跨膜受体蛋白酪氨酸激酶信号转导、各种蛋白的磷酸化、细胞增殖等生物过程,通过蛋白激酶活性、核受体活性、激素结合等分子功能发挥作用,并且与病毒感染、胰腺癌、乙型肝炎、前列腺癌、肝细胞癌、非小细胞肺癌等疾病相关。结论该方法初步揭示了香叶醇抑制结肠癌的潜在靶点,为中药治疗结肠癌提供理论依据。

Objective To study inhibition of colon cancer mechanism of geraniol based on network pharmacology and molecular docking.Methods The 2D and 3D structures of geraniol were obtained by PubChem,and the structures of geraniol were determined by Swiss Target Prediction,the target information of geraniol monomer was obtained by prediction platform,and the disease targets related to colon cancer were obtained by GeneCards database,OMIM database and TTD database.The differential genes of colon cancer were obtained by analyzing gene chip through gene expression omnibus(GEO)database.The network analysis map was constructed by Cytoscape3.8.2 software,and the intersection genes were analyzed by gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)by Metascape pathway analysis,molecular docking and literature validation.Results There were 111 target genes corresponding to geraniol,396cross genes between GEO database and public database,and 18 cross genes between geraniol and colon cancer;among them,epithelial growth factor receptor(EGFR),mitogen-activated protein kinase 8(MAPK8),mitogen activated protein kinase kinase 1(MAP2K1),MAPK14,androgen receptor(AR),Tyrosine-protein kinase JAK2,progesterone receptor(PGR),G2/mitotic specific cyclin B 1(CCNB1)were the key targets,mainly involved in Janus kinase/signal transducer and activator of transcription(JAK/STAT),mitogen-activated protein kinase(MAPK)and other cancer-related signaling pathways,transmembrane receptor protein tyrosine kinase signal transduction,and phosphorylation of various proteins Biological processes such as chemonucleosis and cell proliferation play a role through protein kinase activity,nuclear receptor activity,hormone binding and other molecular functions,and were associated with viral infection,pancreatic cancer,hepatitis B,prostate cancer,hepatocellular carcinoma,non-small cell lung cancer and other diseases.Conclusion The method preliminarily revealed the potential target of geraniol in inhibiting colon cancer,and provided theoretical basis for the treatment of colon cancer with traditional Chinese medicine.