基于网络药理学探讨芪术郁灵汤治疗食管癌的分子生物学机制研究  

Network pharmacology⁃based elucidation of molecular biological mechanisms of Qizhu Yuling decoction for treatment of esophagus cancer

作　　者：许博文 李娟 李杰[1] 张潇潇[1] 吴静远 曹璐畅 但文超 XU Bo-wen;LI Juan;LI Jie;ZHANG Xiao-xiao;WU Jing-yuan;CAO Lu-chang;DAN Wen-chao(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]北京中医药大学,北京100029

出　　处：《海南医学院学报》2021年第18期1390-1399,共10页Journal of Hainan Medical University

基　　金：国家自然科学基金资助项目(81774289);北京市科技计划重大基金资助项目(D161100005116004);中国中医科学院院级自主选题(ZZ11-028)。

摘　　要：目的:基于网络药理学探讨芪术郁灵汤治疗食管癌的活性成分、作用靶点及分子机制研究。方法:采用TCMSP检索及查找文献筛选抗食管癌活性的芪术郁灵汤的活性化合物,并经DrugBank查找及Swiss Target Prediction预测药物靶点,从GeneCards、OMIM、DrugBank、TTD、DisGeNET等数据库获得食管癌相关基因,抽取交集网络获得候选基因。以Cytoscape构建“中药⁃化合物⁃靶点⁃疾病”网络,以STRING构建PPI网络并筛选核心网络模块,在Metascape行GO和KEGG富集分析,并构建“通路⁃基因”网络以筛选关键靶基因。结果:共获有效成分47个(黄芪19个、莪术4个、白术11个、郁金9个、威灵仙5个、石见穿5个),候选基因297个,GO功能2413个和KEGG通路119条。结论:芪术郁灵汤治疗食管癌的有效成分为槲皮素、山柰酚、甘氨酸、熊果酸等,潜在靶点为AKT1、MAPK1、MAPK3、PIK3R1和RELA等,GO包括氧化应激、细胞周期、凋亡和死亡等,KEGG涉及典型的癌症途径、MAPK、NF⁃κB和PI3K⁃Akt通路等。本研究揭示了芪术郁灵汤治疗食管癌的分子生物学机制,推测潜在靶点的功能集中在多条信号通路的交互作用上,能拮抗食管癌的增殖、侵袭、转移与复发,以改善患者预后,此为后续中药新药研发、临床应用与实验研究提供了新的证据。Objective:To investigate the active compounds,key targets and molecular mechanism of Qizhu Yuling decoc⁃tion in the treatment of esophageal carcinoma based on network pharmacology.Methods:The active compounds of Qizhu Yuling decoction with anti⁃esophageal cancer activity were screened by TCMSP and literature search,and the drug targets were searched by DrugBank and predicted by Swiss Target Prediction.The esophageal cancer⁃related genes were obtained from GeneCards,OMIM,DrugBank,TTD,DisGeNET,and the intersection network was selected to obtain candidate genes.The"herb⁃com⁃pound⁃target⁃disease"network was constructed with Cytoscape,the PPI network was constructed in STRING and core network modules were screened.Gene ontology and KEGG enrichment analysis was performed by using Metascape,and the"path⁃way⁃gene"network was constructed to further screen key targets.Results:A total of 47 active compounds(19 Astragalus,4 Zedo⁃ary turmeric,11 Atractylodes macrocephala,9 Curcuma longa,5 Clematis root,and 5 Salvia chinensis),297 candidate genes,2413 GO and 119 KEGG pathways were obtained.Conclusion:The active compounds of Qizhu Yuling decoction in the treatment of esophageal cancer are quercetin,kaempferol,glycine and ursolic acid.The potential targets are AKT1,MAPK1,MAPK3,PIK3R1 and RELA.GO involves oxidative stress,cell cycle,apoptosis and cell death,and KEGG involves typical cancer path⁃ways,MAPK,NF⁃κB and PI3K⁃Akt signaling pathways.This study reveals the molecular biological mechanism of Qizhu Yuling decoction in the treatment of esophageal cancer,and speculates that the function of potential targets focuses on the interaction of multiple signaling pathways,which can antagonize the proliferation,invasion,metastasis and recurrence of esophageal cancer and improve the prognosis of patients.This study provides new evidence for subsequent new drug development,clinical application and experimental study.

关 键 词：芪术郁灵汤 食管癌 网络药理学 机制研究 新药研发 

分 类 号：R285[医药卫生—中药学]