基于网络药理学和分子对接技术探讨苜蓿素抗结肠癌作用机制  

Study on the Mechanism of Tricin in Colon Cancer Based on Network Pharmacology and Molecular Docking Technology

作　　者：刘利艳 温世伟[1] 刘卫云 周艳 徐彭[4] Liu Liyan;Wen Shiwei;Liu Weiyun;Zhou Yan;Xu Peng(College of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;Department of Pharmacy,Jiangxi Provincial Cancer Hospital,Nanchang 330029,China;Department of Pediatrics,Xinyu People's Hospital,Xinyu 338000,China;Laboratory Animal Science and Technology Center,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学药学院,南昌330004 [2]江西省肿瘤医院药剂科,南昌330029 [3]新余市人民医院儿科,新余338000 [4]江西中医药大学实验动物科技中心,南昌330004

出　　处：《世界科学技术-中医药现代化》2020年第4期978-985,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：江西省卫生计生委中医药科技课题(2014A026):苜蓿素抗结肠癌作用及机制探讨,负责人:刘利艳

摘　　要：目的利用网络药理学和分子对接技术分析方法,建立苜蓿素抗结肠癌的"化合物-靶标-疾病-通路"作用网络,来探索苜蓿素抗结肠癌作用机制。方法通过PubChem和swisstarget数据库来寻找苜蓿素的作用靶标,用Therapeutic target数据库寻找结肠癌疾病的可能相关靶标。采用bioinformatics数据库将两者交叉的靶点进行合并。接着运用String数据库结合Cytoscape软件绘制结肠癌靶点的蛋白相互作用网络,通过david数据库对通路进行富集与分析,采用DISCOVERY STUDIO软件对苜蓿素与作用靶点进行分子对接验证。结果苜蓿素与结肠癌交叉共有靶点有69个,经通路分析发现共涉及通路共有55条,有21条通路与癌症相关。分子对接显示苜蓿素分别能与AKT1、EGFR和ESR1蛋白稳定结合。并分别通过氨基酸残基LYS A276、THR A160、THR A195氢键连接、GLY A159、GLY A294、GLU A198碳氢键等连接与AKT1稳定结合;通过THR A570、METB576碳氢键、ALA A573 PI氢键、VAL A575、PRO A572PI烷基、GLY A574 PI酰基与EGFR能稳定对接;通过GLY B457、ARG A434氢键连接、TYR B459、ALA A430、SER A433、ASN B455碳氢键连接等与ESR1稳定结合。结论本研究揭示了苜蓿素治疗结肠癌具有多靶点、多通路的潜在机制,为后续的研究提供方向与思路。Objective To explore the mechanism of action of tricin against colon cancer by using network pharmacology and molecular docking techniques to establish a network of"compound-target-disease-pathway"of tricin against colon cancer.Methods The PubChem and swisstarget databases were used to find the target of tricin,and the Therapeutic target database was used to find possible targets for colon cancer.The bioinformatics database was used to combine the targets that two crossed.Then String database combined with Cytoscape software was used to map the protein interaction network of colon cancer target,enrich and analyze the pathway through david database,and use DISCOVERY STUDIO software to perform molecular docking verification between tricin and target.Results There were 69 common targets for the intersection of tricin and colon cancer.A total of 55 pathways were involved in the pathway analysis,and 21 pathways were associated with cancer.Molecular docking showed that tricin can stably bind proteins AKT1,EGFR and ESR1,respectively,which bind to AKT1 through amino acid residues LYS A276,THR A160,THR A195 hydrogen bond,GLY A159,GLY A294,GLU A198 hydrocarbon bond and so on;through THR A570,MET B576 hydrocarbon bond,ALA A573 PI hydrogen bond VAL A575,PRO A572 PI alkyl,GLY A574 blind to EGFR stably;stable binding to ESR1 through GLY B457,ARG A434 hydrogen bonding,TYR B459,ALA A430,SER A433,ASN B455 hydrocarbon bonding respectively.Conclusion This study reveals the potential mechanism of tricin in the treatment of colon cancer with multiple targets and multiple pathways,providing direction and ideas for subsequent research.

关 键 词：网络药理学 分子对接 苜蓿素 结肠癌 

分 类 号：R273[医药卫生—中西医结合]