[1] HU Yaqi GAO Lei HAO Wanshan JIANG Min,.Exploration of Action Mechanism of “Huangqi-Banxia” Drug Pair in Treatment of Nonsmall Cell Lung Cancer [J]. Modern Traditional Chinese Medicine, 2023, (03): 106-117. [doi: 10.13424/j.cnki.mtcm.2023.03.020]
Exploration of Action Mechanism of “Huangqi-Banxia” Drug Pair in Treatment of Nonsmall Cell Lung Cancer
- Article number:
- 1672-0571(2023)03-0106-12
- Keywords:
- Key words:“Huangqi-Banxia” drug pair; Non small cell lung cancer; Network pharmacology; Molecular docking
- ZTFLH:
- R282.6
- Code:
- A
- Abstract:
- Abstract：Objective To explore the mechanism of action of HuangqiBanxia in the treatment of nonsmall cell lung cancer (NSCLC) using network pharmacology methods and molecular docking technology.Methods Through literature search and TCMSP database screening,the main components and targets of the “Huangqi-Banxia” drug pair were identified.NSCLC related targets were obtained from GeneCards,PharmaGKB,DrugBank,and OMIM databases.The “Traditional Chinese Medicine-Component-Target” and “Traditional Chinese Medicine-Component-Target-Disease” interaction networks were constructed using Cytoscape software；The STRING database was used to construct a protein interaction network,and the key targets of “Huangqi-Banxia” drugs for NSCLC were screened according to topology parameters；Conduct GO functional enrichment and KEGG pathway analysis on key targets,and construct a “component target pathway” network diagram.Use Auto Dock Vina 1.1.2 to connect the main active ingredients obtained with key targets,and use PyMOL software to visualize the results.Results A total of 33 active ingredients were obtained from the “Huangqi-Banxia” drug pair,which acted on 227 potential targets,1253 NSCLC targets,and 97 key targets were identified through topological analysis.Among them,48 targets with degree values ≥ the median,including TP53,AKT1,CASP3,JUN,etc.GO function enrichment analysis shows that biological processes mainly involve cytokine mediated signal pathways,positive regulation of gene expression,and positive regulation of RNA polymerase II promoter transcription；The enrichment analysis of KEGG pathway mainly includes pathways in cancer pathway,tumor necrosis factor signaling pathway,PI3K Akt pathway,etc.The molecular docking results show that the drug “Huangqi-Banxia” has good binding ability to the main active compounds and five core targets.Conclusion The “HuangqiBanxia” drug pair may act on TP53,AKT1,CASP3,JUN,VEGFA and other related targets through the main active ingredients such as quercetin,kaempferol,and baicalin,interfering with signaling pathways such as Pathways in cancer,tumor necrosis factor,and PI3KAkt,synergistically producing and regulating tumor cell cycle,mediating tumor cell apoptosis,inhibiting its proliferation,differentiation,and metastasis to prevent and treat NSCLC.
References:
［1］World Health Organization.Cancer fact sheets，lung cancer.2020.Available at：https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.Accessed December，2020.
［2］Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA:A Cancer Journal for Clinicians,2021,71(3):209-249.
［3］周永慧,陈鸿志,李燕.免疫检查点抑制剂联合放化疗在晚期非小细胞肺癌治疗中的研究进展［J］.临床肿瘤学杂志,2021,26(10):947-954.
［4］Arbour KC,Riely GJ.Systemic therapy for locally advanced and metastatic nonsmall cell lung cancer:a review［J］.JAMA,2019,322(8):764-774.
［5］Schneider BJ,Naidoo J,Santomasso BD,et al.Management of immunerelated adverse events in patients treated with immune checkpoint inhibitor therapy:ASCO guideline update［J］.J Clin Oncol,2021,39(36):4073-4126.
［6］李春波,田菲.基于扶正祛邪治法论恶性肿瘤的中西医结合治疗［J］.内蒙古中医药,2020,39(7):149-151.
［7］何菊,杨涛,戴彩艳,等.基于复杂网络分析名老中医治疗肺癌的核心病机及用药规律［J］.世界科学技术中医药现代化,2021,23(5):1478-1483.
［8］孙牧,牛春风,旋静.晚期非小细胞肺癌病机初探［J］.世界最新医学信息文摘,2019,19(65):219-220.
［9］蒋晨露,师瑞瑞,孟庆娥,等.从“益气养阴、化痰散结”复法论治晚期肺癌析要［J］.江苏中医药,2020,52(1):76-78.
［10］王子寿,薛红.神农本草经［M］.成都:四川科学技术出版社,2008.
［11］陶弘景.本草经集注:辑校本［M］.尚志钧,尚元胜辑校.北京:人民卫生出版社,1994.
［12］陆婷婷,柯玲玲.黄芪多糖靶向肿瘤微环境的抗肿瘤作用机制［J］.江西中医药大学学报,2019,31(1):107-111.
［13］王莉新,吴文斌,胥孜杭,等.黄芪甲苷通过诱导M1型巨噬细胞极化发挥抗肿瘤作用的机制［J］.中国实验方剂学杂志,2019,25(14):19-24.
［14］罗强,梁晓宇,刘鑫,等.半夏化学成分及药理作用研究进展［J］.特产研究,2020,42(5):54-60.
［15］魏思媛,刘云,孙琴,等.基于网络药理学研究白术黄芪药对抗胃癌作用机制［J］.现代中药研究与实践,2022,36(1):80-85.
［16］杨倩宇,王茜,赵森,等.黄芪莪术影响HIF-1α/VEGF抑制肺癌血管生成相关信号通路的网络药理学研究［J］.中华中医药杂志,2022,37(1):425-430.
［17］陆璐,杨兵,唐东昕.基于网络药理学探讨“黄芪-当归”药对防治肿瘤疾病的物质基础及作用机制研究［J］.贵州中医药大学学报,2021,43(5):30-36.
［18］温芳,舒鹏.黄芪党参药对治疗胃癌的网络药理学研究［J］.中华中医药学刊,2021,39(2):89-94,267.
［19］刘梓燊,杨国旺.基于网络药理学分析“黄芪―白术”治疗肺癌的作用机制［J］.中山大学学报(自然科学版),2020,59(5):134-143.
［20］Hopkins AL.Network pharmacology:the next paradigm in drug discovery［J］.Nature Chemical Biology,2008,4(11):682-690.
［21］Ru JL,Li P,Wang JN,et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines［J］.Journal of Cheminformatics,2014,6(1):13.
［22］Lee WY,Lee CY,Kim YS,et al.The methodological trends of traditional herbal medicine employing network pharmacology［J］.Biomolecules,2019,9(8):362.
［23］Yang YF,Li Y,Wang JH,et al.Systematic investigation of Ginkgo biloba leaves for treating cardiocerebrovascular diseases in an animal model［J］.ACS Chemical Biology,2017,12(5):1363-1372.
［24］Apweiler R,Bairoch A,Wu CH,et al.UniProt:the universal protein knowledgebase［J］.Nucleic Acids Research,2004,32(suppl_1):D115-D119.
［25］Safran M,Rosen N,Twik M,et al.Practical Guide to Life Science Databases［M］.Tokyo:Springer Singapore,2022:27-56.
［26］WhirlCarrillo M,Huddart R,Gong L,et al.An evidencebased framework for evaluating pharmacogenomics knowledge for personalized medicine［J］.Clinical Pharmacology and Therapeutics,2021,110(3):563-572.
［27］Wishart DS,Feunang YD,Guo AC,et al.DrugBank 5.0:a major update to the DrugBank database for 2018［J］.Nucleic Acids Research,2017,46(D1):D1074-D1082.
［28］Amberger JS,Hamosh A.Searching online Mendelian inheritance in man (OMIM):a knowledgebase of human genes and genetic phenotypes［J］.Current Protocols in Bioinformatics,2017,58(1):1.2.1-1.2.12.
［29］Shannon P,Markiel A,Ozier O,et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks［J］.Genome Research,2003,13(11):2498-2504.
［30］Szklarczyk D,Gable AL,Nastou KC,et al.The STRING database in 2021:customizable protein-protein networks,and functional characterization of user-uploaded gene/measurement sets［J］.Nucleic Acids Research,2020,49(D1):D605-D612.
［31］Wheeler DL,Barrett T,Benson DA,et al.Database resources of the national center for biotechnology information［J］.Nucleic Acids Research,2007,36(suppl_1):D13-D21.
［32］Berman HM.The protein data bank［J］.Nucleic Acids Research,2000,28(1):235-242.
［33］段金廒,宿树兰,唐于平,等.中药药对配伍组合的现代认识［J］.南京中医药大学学报,2009,25(5):330-333.
［34］徐浩,刘磊,楼招欢,等.中医“药对”治疗癌症的研究进展［J］.中华中医药杂志,2018,33(10):4533-4538.
［35］朱震亨.丹溪心法［M］.沈阳:辽宁科学技术出版社,1997.
［36］谢丹枫,王能,陈紫莹,等.基于数据挖掘的国家名老中医抗肿瘤用药规律及核心复方解析［J］.世界中医药,2020,15(18):2726-2734.
［37］宋清雅,耿鑫,于宗良,等.吴煜教授治疗脾肾两虚型胃癌的用药规律研究［J］.湖南中医药大学学报,2021,41(9):1400-1406.
［38］杨柱,唐东昕,郭斌,等.刘尚义治疗肿瘤用药经验数据挖掘分析［J］.中医杂志,2016,57(19):1641-1645.
［39］赵惠,王志英,周仲瑛.周仲瑛从痰辨治恶性肿瘤用药分析［J］.中医杂志,2015,56(9):740-744.
［40］吴洪皓,杨华,吴鹏.槲皮素对A549细胞PI3K/Akt信号通路及肿瘤恶性特征的调控机制［J］.中成药,2021,43(12):34763479.
［41］钱麒钰,袁改利,马珊珊,等.槲皮素通过miR101/EZH2轴介导的EMT途径改善NSCLC吉西他滨耐药的机制研究［J］.天津医药,2022,50(2):125-130.
［42］赵存玲,郭风龙,谈燕燕,等.槲皮素通过EMT途径抑制H3122细胞迁移［J］.河北医药,2019,41(2):170-173.
［43］Kim TW,Lee SY,Kim M,et al.Kaempferol induces autophagic cell death via IRE1JNKCHOP pathway and inhibitionof G9a in gastric cancer cells［J］.Cell Death & Disease,2018,9(9):875.
［44］林小聪,刘新光,陈小文,等.山奈酚抑制蛋白激酶CK2活性［J］.中国生物化学与分子生物学报,2006,22(11):894-901.
［45］雷晓青,陈鳌,刘毅,等.山萘酚药理作用的研究进展［J］.微量元素与健康研究,2017,34(2):61-62.
［46］杨生辉,黄琰菁,莫安薇,等.山奈酚通过调控miR21抑制非小细胞肺癌A549细胞增殖的研究［J］.中国现代应用药学,2020,37(13):1557-1562.
［47］张敬,史晓宇,孟玮,等.山萘酚通过下调ERRα抑制非小细胞肺癌A549细胞的侵袭和迁移［J］.中国肿瘤生物治疗杂志,2018,25(12):1230-1236.
［48］朱亚南,杨七妹,张硕,等.黄芩苷与黄芩素药理作用及机制研究进展［J］.时珍国医国药,2020,31(4):921-925.
［49］Hanahan D,Weinberg RA.Hallmarks of cancer:the next generation［J］.Cell,2011,144(5):646-674.
［50］Fernandes JV,Cobucci RNO,Jatobá CAN,et al.The role of the mediators of inflammation in cancer development［J］.Pathology Oncology Research:POR,2015,21(3):527-534.
［51］单慧,杜胤骁,白鹤群,等.黄芩素的研发进展及其临床药理学［J］.中国临床药理学与治疗学,2020,25(6):701-708.
［52］张刘莲,巫梦雪,王茜茜,等.野黄芩素通过miRNA496和基质细胞衍生因子1对子宫颈癌细胞增殖及迁移的影响［J］.肿瘤研究与临床,2022,34(3):161-165.
［53］于开文,于泳,金铁峰,等.黄芩素对肺癌A549细胞的抗增殖作用及机制［J］.延边大学医学学报,2020,43(4):260-263.
［54］邓帅,高峰,田青.黄芩素对人肺癌细胞A549耐顺铂株顺铂细胞毒性及Akt/NF-κB信号通路关系分析［J］.四川中医,2018,36(8):50-53.
［55］Kim SH,Ezhilarasan R,Phillips E,et al.Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-κBdependent manner［J］.Cancer Cell,2016,29(2):201-213.
［56］Kim JS,Turbov J,Rosales R,et al.Combination simvastatin and metformin synergistically inhibits endometrial cancer cell growth［J］.Gynecologic Oncology,2019,154(2):432-440.
［57］甘新天,李哲宏,金宇.VEGFA、Ang-2在肿瘤生长及转移中作用的研究进展［J］.肿瘤预防与治疗,2022,35(2):194-201.
［58］张亚非,何伟娜,庞敏,等.雌激素及其受体在C57BL/6小鼠Lewis肺癌发生发展中的作用［J］.临床肿瘤学杂志,2020,25(8):673-678.
［59］赵文钺,刘璐,王黎明,等.雌激素调控miRNA在非小细胞肺癌发生发展及预后的分子机制［J］.解剖科学进展,2020,26(3):354-356,360.
［60］靳科,凌丰宇,李明.ERα和ERβ高表达与非小细胞肺癌预后的关系［J］.山西医科大学学报,2019,50(2):181-188.
［61］黄玲玲,周懿雯,平毅.低氧诱导因子-1在妇科恶性肿瘤中的研究进展［J］.现代肿瘤医学,2021,29(15):2745-2748.
［62］金烨,颜海豪,代璐,等.缺氧诱导因子-1在胃癌中的研究进展［J］.中国临床研究,2021,34(3):405-408.
［63］王宏宇,刘晓玲.缺氧诱导因子-1(HIF-1)在鼻咽癌发病机制中的研究进展［J］.内蒙古医科大学学报,2020,42(1):100-101,105.
［64］李彦,顾泽鑫,孟祥茹,等.TNF-α通过NF-κB增强Th9细胞分化抑制肺癌细胞生长［J］.免疫学杂志,2022,38(3):228-233.
［65］Mnnel DN,Rüschoff J,Orosz P.The role of TNF in tumour growth and metastasis［J］.Research in Immunology,1993,144(5):364-369.
［66］王蓉,潘思思,宋霞.晚期非小细胞肺癌EGFR-TP53共突变的研究进展［J］.中国肺癌杂志,2022,25(3):174-182.
Memo
基金项目：国家自然科学基金面上项目（82174458）；国家重点研发计划项目（2018YFC1705100）； 北京中医药大学基本科研业务费重点攻关项目（2020-JYB-ZDGG-123）