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作 者:徐亚晨 谢毅强[2] 肖曼 张瑞 孙早喜[1] XU Yachen;XIE Yiqiang;XIAO Man;ZHANG Rui;SUN Zaoxi(Department of Hepatobiliary Surgery,the First Affiliated Hospital,Hainan Medical University,Hainan Province,Haikou570102,China;College of Traditional Chinese Medicine,Hainan Medical University,Hainan Province,Haikou571199,China)
机构地区:[1]海南医学院第一附属医院肝胆外科,海南海口570102 [2]海南医学院中医学院,海南海口571199
出 处:《中国医药导报》2020年第29期123-127,146,F0004,共7页China Medical Herald
基 金:国家自然科学基金资助项目(81860836);海南省重点研发项目(ZDYF2016116)。
摘 要:目的利用网络药理学技术与平台,挖掘半枝莲治疗胰腺癌的作用机制。方法基于TCMSP、NPASS、HIT、TCMID、TCM-ID及中国知网、万方数据知识服务平台、维普网、科学引文索引(SCI)、PubMed等数据库,检索半枝莲活性成分,检索时限为1971年6月—2019年10月。利用预测平台获取并筛选各组分靶基因,维恩分析筛选成分靶基因与胰腺癌特异性基因交互基因,通过成分-靶点-疾病交联确定重要成分及核心靶点,利用基因本体注释(GO)分析及京都基因与基因组百科全书(KEGG)信号通路富集分析半枝莲治疗胰腺癌的分子机制。结果获得半枝莲类药成分24种,提取交互基因73个,筛选出黄芩素、汉黄芩素、黄芩苷、槲皮素、豆甾醇5种重要成分及AKT1、HSP90A1、肿瘤坏死因子、ESR1、表皮生长因子受体、转录后基因沉默2、SRC、基质金属蛋白酶9、基质金属蛋白酶2、AR在内的10个核心靶点。GO功能富集于细胞凋亡、炎症与氧化应激反应的调节,参与蛋白质、ATP酶、DNA链特异性结合等。KEGG富集于癌症、胰腺癌、癌症蛋白多糖、Ras、磷脂酰肌醇-3-激酶-蛋白激酶B途径信号通路等。结论半枝莲可能通过多类靶点,调控多条信号通路,影响多重细胞的功能,从而起到治疗胰腺癌的作用,这也为临床发掘治疗胰腺癌的替代药物提供了理论支撑。Objective To study the mechanism of action of Scutellariae Barbatae Herba in treating pancreatic cancer by using network pharmacology.Methods Based on TCMSP,NPASS,HIT,TCMID,TCM-ID,CNKI,WANFANG DATA,CQVIP,Science Citation Index(SCI),PubMed databases.The active constituents of Scutellariae Barbatae Herba were searched from June 1971 to October 2019.The prediction platform was used to acquire and screen target genes.Venn analysis was used to screen interaction genes between component target genes and pancreatic cancer specific genes,then determined the key targets of the drug through drug-target-disease cross-linking.Then fully utilized gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)signal pathway enrichment to analyze molecular mechanism of Scutellariae Barbatae Herba in treating the disease.Results A total of 24 kinds of drug-like compounds were obtained,73 target genes were determined,five core components including baicalein,wogonin,baicalin,quercetin,stigmasterol,and ten key targets such as AKT1,HSP90A1,tumor necrosis factor,ESR1,epidermal growth factor receptor,post-transcriptional gene silencing 2,SRC,matrix metalloproteinase 9,matrix metalloproteinase 2 and AR were screened out.GO enriched in the regulation of apoptosis,inflammation and oxidative stress,and were involved in the specific binding of proteins,ATPases and DNA.KEGG enriched in cancer,pancreatic cancer,cancer proteoglycan,Ras,phosphatidylinositol-3-kinase-protein kinase B pathway.Conclusion Scutellariae Barbatae Herba may regulate multiple signaling pathways through multiple types of targets,affecting multiple function of cells,thus playing a role in the treatment of pancreatic cancer.
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