基于网络药理学和分子对接探讨芪术抗癌方治疗原发性肝癌的分子机制  

The molecular mechanism of Qizhu anti-cancer prescription in treatment of primary liver cancer based on network pharmacology and experimental verification

作　　者：马梦情 孙嘉玲 胡锐 冯文杏 韩志毅[1,2] 孙新锋[1,2] 马文峰[1,2] 张卫[1,2] 陈剑平[1,4] 周小舟[1,2] MA Meng-qing;SUN Jia-ling;HU Rui;FENG Wen-xing;HAN Zhi-yi;SUN Xin-feng;MA Wen-feng;ZHANG Wei;CHEN Jian-ping;ZHOU Xiao-zhou(School of the Fourth Clinical Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;National Key Specialty of Clinical Liver Disease(Traditional Chinese Medicine)of Shenzhen Traditional Chinese Medicine Hospital,Shenzhen Guangdong 518033,China;School of Chinese Medicine,Macao University of Science and Technology,Macao 999078,China;Key Laboratory of Traditional Chinese Medicine Formulation Research,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen Guangdong 518033)

机构地区：[1]广州中医药大学第四临床医学院,广东广州510006 [2]深圳市中医院国家临床肝病(中医)重点专科,广东深圳518033 [3]澳门科技大学中医药学院,中国澳门999078 [4]深圳市中医院中药制剂研究重点实验室,广东深圳518033

出　　处：《中国药理学通报》2023年第12期2369-2377,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82205209);深圳市科技计划项目(No JCYJ20210324120405015);广东省中医药局项目(No 20202152)。

摘　　要：目的运用网络药理学和分子对接探究芪术抗癌方(Qizhu anti-cancer prescription,QZACP)治疗原发性肝癌的作用机制。方法根据TCMSP数据库及GeneCard等疾病数据库寻找药物及原发性肝癌(primary liver cancer,PLC)相关靶点,应用Cytoscape 3.9.1和String平台分别进行关键化合物和靶点的筛选,并构建中药-关键成分-靶点网络关系图;并通过DAVID平台进行GO功能富集分析和KEGG通路富集分析,依托于R 4.1.1软件进行可视化,最后通过CytoNCA插件对核心聚类蛋白进行分析得到核心作用靶点,使用分子对接技术预测活性成分与核心靶点匹配程度以及动物实验进一步探索QZACP的药效机制。结果QZACP治疗PLC的活性成分有可能是槲皮素、甘草酸苷、白玉兰素B等;潜在靶标为STAT3、EGFR、AKT1等;相关的通路主要有PI3K-Akt信号通路、MAPK信号通路等;分子对接结果显示,关键化学成分与核心靶点都具有良好的结合构象,另外,通过体内实验验证了QZACP能够抑制裸鼠肿瘤的生长,并降低STAT3、EGFR、AKT1等蛋白表达量。结论QZACP可能对PLC治疗存在一定的积极意义,可能与调控PI3K/Akt信号通路有关。Aim To investigate the mechanism of Qizhu anti-cancer prescription(QZACP)inthe treatment of primary liver cancer using network pharmacology and molecular docking.Methods Drugs and primary liver cancer(PLC)-related targets were found according to TCMSP database and disease databases such as GeneCard,the key chemical components and core targets were screened by Cytoscape 3.9.1 and String platform respectively,and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9.1.GO functional analysis and KEGG pathway analysis were performed using DAVID platform,visualized by R 4.1.1 software,and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets,and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments.Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin,glycyrrhizin,Denudatin B,isoflavanone,sanguinarol,etc.;the potential targets were STAT3,EGFR,AKT1 etc.;the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc.;molecular docking showed that the core compounds had better integrating conformation with the key targets.In addition,QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3,EGFR and AKT1.Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer,which may be related to the regulation of PI3K/Akt signaling pathway.

关 键 词：芪术抗癌方 原发性肝癌 网络药理学 分子对接 信号通路 机制 

分 类 号：R-332[医药卫生] R289.5R319R735.7