基于网络药理学及分子对接探讨散风通窍滴丸治疗鼻咽癌的分子机制  

Molecular mechanism underlying Sanfeng Tongqiao Dripping Pills as a treatment for nasopharyngeal carcinoma based on network pharmacology and molecular docking

作　　者：林子粤 徐咏晴 孙宝清[2] 罗嘉莹[2] Lin Ziyue;Xu Yongqing;Sun Baoqing;Luo Jiaying(Guangzhou Medical University,Guangzhou 510180,China;State Key Laboratory of Respiratory Disease,First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510230,China)

机构地区：[1]广州医科大学,广州510180 [2]广州医科大学附属第一医院呼吸疾病国家重点实验室,广州510230

出　　处：《中华生物医学工程杂志》2022年第6期601-609,共9页Chinese Journal of Biomedical Engineering

摘　　要：目的采用网络药理学和分子对接方法探讨散风通窍滴丸治疗鼻咽癌的潜在作用机制。方法在BATMAN-TCM数据库中寻找散风通窍滴丸的潜在作用通路,并从TCMSP及UniProt数据库筛选出散风通窍滴丸各活性成分可能存在的靶点,GeneCards数据库挖掘鼻咽癌相关靶点基因,通过STRING数据库、Cytoscape软件、EVENN网站、BATMAN-TCM数据库进行网络可视化,最后采用PubChem化合物、RCSB蛋白质数据库、AutoDockTools、Autodock Vina以及PyMoL软件进行分子对接进一步探究其相互作用的可能性。结果散风通窍滴丸可以对癌症起作用,经筛选在鼻咽癌中发现13个治疗的潜在靶点:NCOA1、NCOA2、HSP90AA1、BAX、PTGS2、JUN、PIK3CG、DPP4、BCL2、PGR、CASP3、CHRNA7和NOS2;对应的靶蛋白为CREBBP、ITGB1、RAC1、HDAC1、STAT1和JAK2,作用通路主要涉及雌激素信号通路,白细胞介素17信号通路和一些凋亡信号通路;多维网络分析结果提示散风通窍滴丸治疗鼻咽癌的3个靶基因为PTGS2、NCOA1、PIK3CG,有6条代谢途径参与该过程,代谢途径主要与凋亡和抗炎症反应相关。分子对接结果提示治疗靶点PTGS2和NCOA2与药物潜在活性成分紧密结合。结论散风通窍滴丸可能通过参与调节激素分泌、促进肿瘤细胞凋亡、抑制肿瘤细胞增殖、抗炎症反应等治疗鼻咽癌。Objective To investigate the potential mechanism of action underlying Sanfeng Tongqiao Dripping Pills as a treatment for nasopharyngeal carcinoma(NPC)by using network pharmacology and molecular docking.Methods The potential pathways by which Sanfeng Tongqiao Dripping Pills acts on NPC were searched in BATMAN-TCM database.The possible targets of each active ingredient against NPC in Sanfeng Tongqiao Dripping Pills were screened from TCMSP and UniProt databases.Nasopharyngeal carcinoma-related target genes were obtained by data-mining of GeneCards database.The STRING database,Cytoscape software,EVENN website,and BATMAN-TCM database were used for visualization of the PPI network.Finally,PubChem database,RCSB protein data bank,AutoDockTools,Autodock Vina,and PyMoL were used for molecular docking to further explore the possibility of the interactions in the PPI network.Results Sanfeng Tongqiao Dripping Pills might work against NPC.Thirteen potential targets were identified in NPC after screening:NCOA1,NCOA2,HSP90AA1,BAX,PTGS2,JUN,PIK3CG,DPP4,BCL2,PGR,CASP3,CHRNA7 and NOS2,to which,the corresponding target proteins were CREBBP,ITGB1,RAC1,HDAC1,STAT1 and JAK2.The pathways mainly involved were the estrogen signaling pathway,interleukin 17 signaling pathway and several apoptosis-related signaling pathways.Our multidimensional network analysis suggested that Sanfeng Tongqiao Dripping Pills as a treatment for NPC acted on 3 target genes(PTGS2,NCOA1 and PIK3CG)via 6 metabolic pathways largely related to cell apoptosis and anti-inflammatory action.Molecular docking suggested that the therapeutic targets PTGS2 and NCOA2 were tightly bound to potential active components of the drug.Conclusion Sanfeng Tongqiao Dripping Pills as a treatment for NPC probably work by participating in regulation of hormone secretion,pro-apoptotic and anti-proliferative effect on tumor cells,and anti-inflammatory actions.

关 键 词：黄芩 细辛 荆芥 羌活 鼻咽癌 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]