基于网络药理学的鸦胆子活性成分抗肿瘤分子机制
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摘要
目的利用网络药理学方法探索鸦胆子抗肿瘤有效成分、潜在靶点及通路,探讨其"多成分-多靶点-多通路"的抗肿瘤作用机制。方法①从中药系统药理学数据库和分析平台中筛选出鸦胆子潜在的15个活性成分,根据DrugBank获取这15个活性成分的158个潜在靶分子。②利用String数据库构建这些靶分子的蛋白质-蛋白质相互作用网络,其中节点度值最高的基因JUN定义为核心基因,利用癌症和肿瘤基因图谱分析其在多个肿瘤中的作用。③利用R语言Cluster profiler包将这些靶分子进行基因功能分析和基因功能富集分析。结果获取了鸦胆子潜在的15个活性成分,158个潜在靶分子及活性成分-靶蛋白网络,并发现了其在多种肿瘤、多种成分、多种通路有着不同的比重和作用。结论网络药理学方法可为解析鸦胆子多成分、多靶点、多通路、多肿瘤的关系网络,阐述其抗肿瘤的分子机制提供思路和方法,为其临床应用提供相应的理论依据。
Objective To investigate the active components,potential targets,and pathways of antitumor activities of Brucea javanica based on network pharmacology,as well as its antitumor mechanism of action involving"multiple components,targets,and pathways".Methods A total of 15 potential active components of Brucea javanica were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and 158 potential target molecules of these 15 active components were obtained from DrugBank.The String database was used to construct the protein-protein interaction(PPI)network of these target molecules.The JUN gene with the highest node degree was defined as the hub gene,and The Cancer Genome Atlas was used to analyze its role in various tumors.The cluster Profiler package in R language was used for gene function analysis and gene set enrichment analysis of target molecules.Results A total of 15 potential active components of Brucea javanica were obtained,with 158 potential target molecules and active component-target protein interaction network,and different proportions and roles for various tumors,components,and pathways were found.Conclusion The method based on network pharmacology provide ideas and methods for analyzing the interaction network of Brucea javanica with various components,targets,pathways,and tumors and elaborating on its antitumor mechanism of action,which lays a theoretical foundation for clinical application in future.
Objective To investigate the active components,potential targets,and pathways of antitumor activities of Brucea javanica based on network pharmacology,as well as its antitumor mechanism of action involving"multiple components,targets,and pathways".Methods A total of 15 potential active components of Brucea javanica were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and 158 potential target molecules of these 15 active components were obtained from DrugBank.The String database was used to construct the protein-protein interaction(PPI)network of these target molecules.The JUN gene with the highest node degree was defined as the hub gene,and The Cancer Genome Atlas was used to analyze its role in various tumors.The cluster Profiler package in R language was used for gene function analysis and gene set enrichment analysis of target molecules.Results A total of 15 potential active components of Brucea javanica were obtained,with 158 potential target molecules and active component-target protein interaction network,and different proportions and roles for various tumors,components,and pathways were found.Conclusion The method based on network pharmacology provide ideas and methods for analyzing the interaction network of Brucea javanica with various components,targets,pathways,and tumors and elaborating on its antitumor mechanism of action,which lays a theoretical foundation for clinical application in future.
引文
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[3]杨凡,闫涵,庞歆桥,等.鸦胆子油联合化学治疗治疗结直肠癌效果的系统评价[J].山东医药,2016,56(13):45-47.
[4]孙琳,赵安聚,魏玉成,等.鸦胆子油治疗中晚期原发性肝癌的研究进展[J].现代中西医结合杂志,2017,26(15):1707-1710.
[5]刘玲,钟世寿.鸦胆子油乳注射液联合化学治疗治疗晚期三阴性乳腺癌临床观察[J].医药前沿,2017,7(14):189-190.
[6]李蓉晖,王德亮.鸦胆子抗肿瘤活性成分与机制研究进展[J].中国中医药资讯,2012,4(3):95.
[7]马青松,庞玉新,杨全,等.鸦胆子的药理作用和抗肿瘤机制研究进展[J].贵州农业科学,2015,43(2):137-140.
[8]袁长胜,陈文.基于TCMSP对玫瑰花黄酮和挥发油防治心血管疾病的协同作用及其机制研究[J].石河子大学学报(自然科学版),2016,34(6):731-734.
[9]石海英,王唯红,王金虎,等.新药研发中类药性概念应用现状的研究分析[J].医药卫生,2017,9(1):289.
[10]LE D H,PHAM V H.HGPEC:a Cytoscape App for prediction of novel disease-gene and disease-disease associations and evidence collection based on a random walk on heterogeneous network[J].BMC Systems Biology,2017(11):61-70.
[11]NATERI A S,SPENCER-DENE B,BEHRENS A.Interaction of phosphorylated c-Jun with TCF4regulates intestinal cancer development[J].Nature,2005,437(7056):281-285.
[12]LIU Y Q,CHEN X R,CHENG R J.et al.The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer[J].Molecular Cancer,2018(17):11-25.
[13]VARFOLOMEEV E,GONCHAROV T,MAECKERH,et al.Cellular inhibitors of apoptosis are global regulators of NF-kappa B and MAPK activation by members of the TNF family of receptors[J].Science Signal,2012,5(216):ra22.
[14]GUO B Q,LU W Q.The prognostic significance of high/positive expression of tissue VEGF in ovarian cancer[J].Oncotarget,2018,9(55):30552-30560.