摘要
目的基于数据挖掘、网络药理学和分子对接分析湖湘欧阳氏杂病流派传承人朱克俭教授治疗肺癌的临床用药规律,并探讨高频药物的抗肿瘤可能机制。方法收集朱克俭临床治疗肺癌的病例,利用IBM SPSS Statistics 20.0软件和Apriori关联规则算法筛选治疗肺癌的高频药物及药对。应用TCMSP、Swiss Target Prediction、OMIM等数据库及相关文献,筛选高频药物的活性成分、潜在靶点,并与肺癌相关靶点作比对,得到肺癌核心靶点,构建“肺癌核心靶点-活性成分-药物”之间网络关系。再运用STRING数据库得到“肺癌核心靶点”互作关系。通过DAVID进行GO与KEGG富集分析;使用Vina对药物关键成分、阳性药吉非替尼与Hub靶点进行分子对接验证,最后用Rstudio做分子热图。结果药物使用频次与频率筛选得到前5位高频药物依次为黄芪、臭牡丹、桔梗、鱼腥草、仙鹤草。高频药对有“黄芪-臭牡丹”“黄芪-桔梗”等。数据库筛选得到5味高频药物共含有83个活性成分,760个潜在靶点,40个肺癌核心靶点。GO分析结果显示核心靶点主要与细胞凋亡、细胞增殖、蛋白质自磷酸化等177条生物过程有关;KEGG分析显示核心靶点主要涉及肿瘤中信号通路(pathway in cancer)、PI3K-Akt和肿瘤中蛋白聚糖信号通路(proteoglycan in tumor)等63条信号通路。分子对接结果显示12个关键成分与3个Hub靶点具有较好的结合活性。结论湖湘欧阳氏杂病流派善用补脾肺气、解毒抗癌、化痰止咳类中药,通过活性成分槲皮素、芹菜素、木犀草素等多种成分,对TP53、AKT1、VEGFA等多靶点作用,并可能通过影响pathway in cancer、PI3K-Akt和proteoglycan in tumor等多通路起到抗肿瘤的作用,为挖掘高效低毒的抗肺癌复方及化合物奠定了基础。
Objective To analyze the clinical medication rules of Professor ZHU kejian,inheritor of Huxiang OUYANG’s genre of miscellaneous diseases to treat lung cancer Based on data mining,network pharmacology,and molecular docking analysis,and to explone the possible antitumor mechanism of high-frequency drugs.Methods Clinical cases of lung cancer treated by Professor ZHU kejian were collected,and the high-frequency drugs and drug pairs for lung cancer were screened by IBM SPSS Statistics 20.0 software and Apriori association rule algorithm.Databases(TCMSP,Swiss Target Prediction,OMIM,etc)and literatures were used to screen the active ingredients and potential targets of high-frequency drugs,which compared with lung cancer related targets,and the core targets of lung cancer were obtained.The network diagram of“core target of lung cancer-active component-drug”was further constructed.The interaction of“lung cancer-core target”was made by STRING.DAVID was used to conduct GO and KEGG enrichment analysis.Key drug components and positive drug(gefitinib)were respectively docked with Hub target by using Vina for molecular docking verification and finally R Studio was used to make heatmap.Results The top 5 high-frequency drugs were Astragalus membranaceus,Clerodendrum bungei,Platycodon grandiflorum,Houttuynia cordata and Hairyvein agrimonia.High-frequency drug pairs included“Astragalus membranaceus-Clerodendrum bungei”,“Astragalus membranaceus-Platycodon grandiflorum”,etc.From 5 high-frequency drugs screened from the databases,83 components,760 potential targets and 40 core targets of lung cancer were found.GO analysis showed that the core targets were mainly related to 177 biological processes,such as cell apoptosis,cell proliferation,and protein autophosphorylation.KEGG analysis showed that the core targets were mainly involved in 63 signaling pathways,including pathway in cancer,PI3K-Akt and proteoglycan in tumor,etc.Molecular docking suggested that 12 key components had strong interactions with 3 Hub targets.Conclusion Traditional Chinese medicine for tonifying spleen and lung qi,detoxification and anti-cancer,resolving phlegm and relieving cough had been used well in Huxiang OUYANG’s genre of miscellaneous disease.OUYANG’s genre of miscellaneous disease exerted antitumor effect through the action of active components(quercetin,apigenin,luteolin)on multiple targets(TP53,AKT1,VEGFA),and regulation of pathway in cancer,PI3K-Akt signaling Pathway,proteoglycans in cancer etc.The study lay the foundation for further exploration of high-efficiency and lowtoxicity TCM anti-lung cancer prescriptions and compounds.
作者
余娜
王芬
陈巧巧
刘佳俊
黄群富
唐皓
丁长松
朱克俭
YU Na;WANG Fen;CHEN Qiaoqiao;LIU Jiajun;HUANG Qunfu;TANG Hao;DING Changsong;ZHUKejian(School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208 Hunan,China;Chinese Medicine Big Data Analysis Laboratory,Hunan University of Chinese Medicine,Changsha 410208 Hunan,China;Hunan Academy of Traditional Chinese Medicine,Changsha 410006 Hunan,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2022年第8期1071-1082,共12页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
湖南省中医药管理局课题(201935)
湖南省自然科学基金项目(2020JJ5428)
国家重点研发计划项目(2017YFC1703306)
湖南省中医药科研计划重点课题(2020002)
中药现代化研究室,湖南中医药大学中药学一流学科项目(校行科字[2018]3号)
湖南省“国内一流建设学科”中医学开放基金项目。
关键词
肺癌
朱克俭
湖湘欧阳氏杂病流派
用药规律
数据挖掘
网络药理学
分子对接
lung cancer
ZHU Kejian
Hunan OUYANG’s genre of miscellaneous diseases
medication rules
data mining
network pharmacology
molecular docking
