基于网络药理学探讨启膈散治疗食管癌的作用机制

Mechanism of Qige Powder on Esophageal Cancer Based on Network Pharmacology

目的:基于网络药理学方法探讨启膈散治疗食管癌的可能作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)及中药成分数据库(TCMID)筛选并收集启膈散的活性成分及其对应靶标。利用Uniprot数据库获取药物活性成分对应靶标的基因,并与通过人类基因组注释数据库(GeneCards)所获得的人食管癌相关基因做对比,获得启膈散与食管癌重合的潜在作用靶标基因。使用Cytoscape3.6.1软件绘制启膈散的"活性成分-作用靶标"网络图。通过String数据库获取潜在作用靶标之间的互作关系,并导入Cytoscape3.6.1软件构建靶蛋白互相作用网络图。利用DAVID数据库对启膈散治疗食管癌的潜在作用靶标进行Go分类富集分析和KEGG通路富集分析,并运行R语言得到其高级气泡图。结果:从启膈散中共得到88个候选活性成分,包括槲皮素(quercetin)、β-谷甾醇(beta-sitosterol)、木犀草素(luteolin)、丹参酮ⅡA(tanshinone iia)、柚皮素(naringenin)等,142个潜在作用靶标,包括RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)、肿瘤抑制因子(TP53)、白细胞介素-6(IL-6)、重组人半胱天冬酶-3(CASP3)、血管内皮生长因子A(VEGFA)等,主要通路有蛋白酪氨酸激酶/信号转导转录激活因子(Jak-STAT)、磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)、核转录因子(NF-kappa B)、肿瘤抑制基因p53等信号通路。结论:启膈散治疗食管癌的作用机制可能与AKT1、TP53、IL-6、CASP3、VEGFA等靶标以及调节Jak-STAT、PI3K-Akt、MAPK、NF-kappa B、p53等信号通路有关。

Objective:To explore the possible mechanisms of Qige Powder in the treatment of esophageal cancer based on network pharmacology.Methods:The active components and corresponding targets of Qige Powder were screened and collected in the traditional Chinese medicine(TCM)systems pharmacology database(TCMSP)and the Traditional Chinese Medicine Information Database(TCMID).The Uniprot database was used to obtain the target genes of the target components of the drug active ingredients,and compared with the human esophageal cancer related genes obtained by the Human Genome Annotation Database(GeneCards),the potential target genes of Qige Powder and esophageal cancer were obtained.The"candidate active components-targets"network of Qige Powder was built with Cytoscape3.6.1 software.The interaction among the potential targets was obtained through the String database,and the Cytoscape 3.6.1 software was introduced to construct the target protein interaction network map.The Go classification and KEGG pathway enrichment analysis on the potential targets of Qige Powder in the treatment of esophageal cancer were carried out by DAVID database,and the advanced bubble map was obtained by running the R language.Results:A total of 88 candidate active ingredients were obtained from Qige Powder,including quercetin,beta-sitosterol,luteolin,tanshinone iia and naringenin,etc.,as well as 142 potential targets,including RAC-αserine/threonine protein kinase(AKT1),tumor suppressor(TP53),interleukin-6(IL6),recombinant human cysteine Asparagine-3(CASP3)and vascular endothelial growth factor A(VEGFA),etc.The main pathways were protein tyrosine kinase/signal transduction activator(Jak-STAT),phosphatidylinositol-3-kinase(PI3 K-Akt),mitogen-activated protein kinase(MAPK),nuclear transcription factor(NF-kappa B)and tumor suppressor gene p53,etc.Conclusion:The possible mechanism of Qiqi Powder in the treatment of esophageal cancer may be related to the targets of AKT1,TP53,IL6,CASP3 and VEGFA,as well as the regulation of Jak-STAT、PI3 K-Akt、MAPK、NF-kappa B、p53 and other signaling pathways.