
浏览全部资源
扫码关注微信
1.广州中医药大学 第一临床医学院,广州 510000
2.广州中医药大学 第一附属医院,广州 510000
林瑞婷,在读硕士,从事中西医结合肿瘤临床研究,E-mail:353885651@qq.com
林丽珠,博士,教授,主任中医师,博士研究生导师,从事中西医结合治疗恶性肿瘤研究,Email:linlizhu903@139.com
收稿日期:2020-01-01,
网络出版日期:2020-07-23,
纸质出版日期:2020-10-05
移动端阅览
林瑞婷,陈芝强,林丽珠.基于网络药理学探讨桔梗-苦杏仁与肺癌相关分子机制[J].中国实验方剂学杂志,2020,26(19):217-224.
LIN Rui-ting,CHEN Zhi-qiang,LIN Li-zhu.Molecular Mechanism of Platycodonis Radix- Armeniacae Semen Amarum in Treating Lung Carcinoma Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(19):217-224.
林瑞婷,陈芝强,林丽珠.基于网络药理学探讨桔梗-苦杏仁与肺癌相关分子机制[J].中国实验方剂学杂志,2020,26(19):217-224. DOI: 10.13422/j.cnki.syfjx.20201922.
LIN Rui-ting,CHEN Zhi-qiang,LIN Li-zhu.Molecular Mechanism of Platycodonis Radix- Armeniacae Semen Amarum in Treating Lung Carcinoma Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(19):217-224. DOI: 10.13422/j.cnki.syfjx.20201922.
目的
2
基于网络药理学方法筛选桔梗-苦杏仁药对中的活性成分,预测治疗癌症的作用靶点及信号通路,构建多成分-多靶点-多通路的相互作用网络,进一步探究其治疗肺癌的可能作用机制。
方法
2
通过中药系统药理数据库和分析平台(TCMSP)以及文献查阅,检索并收集桔梗-苦杏仁的活性成分及其对应的靶标。利用UniProt数据库和Genecards数据库获得桔梗-苦杏仁治疗肺癌的潜在靶标基因。用Cytoscape 3.6.0软件构建“成分-靶标”网络。结合String数据库及Cytoscape软件中的Generate style from statistics工具,构建蛋白质相互作用网络。通过Systems Dock Web Site网络服务器与桔梗-苦杏仁的活性成分进行分子对接。利用功能注释生物信息学分析平台(DAVID)数据库,对桔梗-苦杏仁的作用靶标进行京都基因与基因组百科全书(KEGG)通路富集分析和基因本体(GO)分类富集分析。
结果
2
共筛选得到桔梗-苦杏仁的14个活性成分,包括acacetin,cis-dihydroquercetin,spinasterol,licochalcone B,luteolin等,和103个作用靶标,包括诱导型一氧化氮合酶蛋白(NOS2),环加氧酶1蛋白(PTGS1),雄激素受体(AR),环加氧酶2蛋白(PTGS2),二肽基肽酶4(DPP4)等,主要涉及prostate cancer,small cell lung cancer,hepatitis B,T cell receptor signaling pathway等信号通路。
结论
2
该研究基于网络药理学的方法预测了桔梗-苦杏仁治疗肺癌的可能的作用机制,为后续的深入研究提供了方向。
Objective
2
To screen out the active components of Platycodonis Radix-Armeniacae Semen Amarum
predict the targets and signaling pathways
construct the "multi-components
multi-targets and multi-pathways" interaction network and further investigate their molecular mechanism for the treatment of lung carcinoma based on network pharmacology.
Method
2
Active components and corresponding targets of Platycodonis Radix-Armeniacae Semen Amarum were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature consultation. Therapeutic targeted genes of Platycodonis Radix-Armeniacae Semen Amarum in the treatment of lung carcinoma were obtained from UniProt database and Genecards database. The "components-targets" network was constructed by using Cytoscape 3.6.0 software
and the protein-protein interactions network was constructed by String database and "Generate Style From Statistics" tool in Cytoscape software. Its molecular docking with active components of Platycodonis Radix-Armeniacae Semen Amarum was carried out by using Systems Dock Web Site network server. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis on the therapeutic targets of Platycodonis Radix-Armeniacae Semen Amarum were performed with the Database for Annotation
Visualization Andintegrated Discovery (DAVID).
Result
2
Fourteen active components of Platycodonis Radix-Armeniacae Semen Amarum were screened out
including acacetin
cis-dihydroquercetin
spinasterol
licochalcone B
and luteolin
et al. One hundred and three therapeutic targets were screened out
including nitric oxide synthase 2 (NOS2)
prostaglandin endoperoxide synthase 1 (PTGS1)
androgen receptor (AR)
prostaglandin endoperoxide synthase 2 (PTGS2)
and dipeptidyl peptidase 4 (DPP4)
et al. Identified signaling pathways mainly involved prostate cancer signaling pathway
small cell lung cancer signaling pathway
hepatitis B signaling pathway and T cell receptor signaling pathway.
Conclusion
2
The possible molecular mechanism of Platycodonis Radix-Armeniacae Semen Amarum for the treatment of lung carcinoma was explored in this study based on network pharmacology
providing the direction for subsequent research.
BRAY F , FERLAY J , SOERJOMATARAM I , et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin , 2018 , 68 ( 6 ): 394 - 424 .
张诗博 , 赵蔚 , 徐世东 . 肺癌晚期免疫综合治疗的研究进展 [J]. 癌症进展 , 2018 , 16 ( 2 ): 144 - 146,174 .
CHEN W , ZHENG R , ZHANG S , et al . Annual report on status of cancer in China, 2010 [J]. Chin J Cancer Res , 2014 , 26 ( 1 ): 48 - 58 .
王保芹 , 王心恒 , 李泽庚 . 中医药治疗肺癌研究进展 [J]. 中医学报 , 2018 , 33 ( 3 ): 371 - 374 .
GOSS P E , STRASSERWEIPPL K , LEEBYCHKOVSKY B L , et al . Challenges to effective cancer control in China, India, and Russia [J]. Lancet Oncol , 2014 , 15 ( 5 ): 489 - 538 .
关念波 , 刘浩 , 林洪生 . 肺癌中医药治疗的研究进展及展望 [J]. 临床肿瘤学杂志 , 2013 , 18 ( 3 ): 264 - 267 .
孙玲玲 , 陶文慧 . 林丽珠治疗肺癌用药规律分析 [J]. 中医学报 , 2015 , 30 ( 1 ): 17 - 19 .
QIAN L , XIE B , WANG Y , et al . Amygdalin-mediated inhibition of non-small cell lung cancer cell invasion in vitro [J]. Int J Clin Exp Pathol , 2015 , 8 ( 5 ): 5363 - 5370 .
XIE Y , DENG W , SUN H , et al . Platycodin D2 is a potential less hemolytic saponin adjuvant eliciting Th1 and Th2 immune responses [J]. Int Immunopharmacol , 2008 , 8 ( 8 ): 1143 - 1150 .
RU J , LI P , WANG J , et al . TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminf , 2014 , 6 ( 1 ): 1 - 6 .
WALTERS W P , MURCKO M A . Prediction of 'drug-likeness' [J]. Adv Drug Delivery Rev , 2002 , 54 ( 3 ): 255 - 271 .
FISHILEVICH S , ZIMMERMAN S , KOHN A , et al . Genic insights from integrated human proteomics in GeneCards [J]. Database , 2016 , 2016 : baw030 .
SZKLARCZYK D , MORRIS J H , COOK H , et al . The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible [J]. Nucleic Acids Res , 2017 , 45 ( 1 ): 362 - 368 .
HSIN K Y , MATSUOKA Y , ASAI Y , et al . SystemsDock: a web server for network pharmacology-based prediction and analysis [J]. Nucleic Acids Res , 2016 , 44 ( W1 ): 507 - 513 .
DENNIS G , SHERMAN B T , HOSACK D A , et al . DAVID: database for annotation, visualization, and integrated discovery [J]. Genome Biol , 2003 , 4 ( 5 ): 3 .
冯解语 , 罗斌 , 董昌盛 , 等 . 田建辉治疗肺癌转移的用药规律 [J]. 湖北中医药大学学报 , 2017 , 19 ( 3 ): 101 - 106 .
卢茵茵 , 庄逸洋 , 黄楚栓 , 等 . 林丽珠治疗肺癌用药规律的数据挖掘研究 [J]. 中医杂志 , 2016 , 57 ( 18 ): 1557 - 1559,1564 .
石元英 , 徐勤 . 黄酮类化合物抗肿瘤作用机制的研究与靶向治疗策略 [J]. 华夏医学 , 2017 , 30 ( 2 ): 164 - 168 .
NAGAPPAN A , LEE H , SARALAMMA V , et al . Flavonoids isolated from induced G 2 /M cell cycle arrest and apoptosis in A549 human lung cancer cells [J]. Oncol Lett , 2016 , 12 ( 2 ): 1394 - 1402 .
马纳 , 李亚静 , 范吉平 . 金合欢素药理研究进展 [J]. 中国现代应用药学 , 2018 , 35 ( 10 ): 1591 - 1595 .
CHIEN S T , LIN S S , WANG C K , et al . Acacetin inhibits the invasion and migration of human non-small cell lung cancer A549 cells by suppressing the p38 α MAPK signaling pathway [J]. Mol Cell Biochem , 2011 , 350 ( 1/2 ): 135 - 148 .
李聪 , 胡强 , 张燕翔 , 等 . 槲皮素的药理学活性研究进展 [J]. 湖北中医杂志 , 2018 , 40 ( 6 ): 63 - 66 .
RAJAVEL T , MOHANKUMAR R , ARCHUNAN G , et al . Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells [J]. Sci Rep , 2017 , 7 ( 1 ): 3418 .
万军 , 车云 , 康宁宁 . 信号通路蛋白Akt1、ERK1/2与HIF-1α在肺癌组织中的表达及其临床意义 [J]. 实用癌症杂志 , 2014 , 29 ( 12 ): 1515 - 1517,1521 .
DEB S P , DEB S . Mutant p53 and MDM2 in cancer volume 85. Lung cancer stem cells, p53 mutations and MDM2 [J]. Subcell Biochem , 2014 , 85 ( 19 ): 359 - 370 .
WU H , LIU H Y , LIU W J , et al . miR‐377‐5p inhibits lung cancer cell proliferation, invasion, and cell cycle progression by targeting Akt1 signaling [J]. J Cell Biochem , 2019 , 120 ( 5 ): 8120 - 8128 .
LI S , MA Y , HOU X , et al . MiR-185 acts as a tumor suppressor by targeting Akt1 in non-small cell lung cancer cells [J]. Int J Clin Exp Pathol , 2015 , 8 ( 9 ): 11854 - 11862 .
吴爱兵 , 黎明春 , 麦宗炯 , 等 . CK2α通过PI3K/Akt/GSK-3 β 信号通路调控肺腺癌A549细胞的侵袭及迁移 [J]. 中国肺癌杂志 , 2017 , 20 ( 4 ): 233 - 238 .
DE SIMONE V , FRANZÈ , E , RONCHETTI G , et al . Th17-type cytokines, IL-6 and TNF- α synergistically activate STAT3 and NF- κ B to promote colorectal cancer cell growth [J]. Oncogene , 2015 , 34 ( 27 ): 3493 - 3503 .
JIN L , WESSELY O , MARCUSSON E G , et al . Prooncogenic factors miR-23b and miR-27b are regulated by Her2/Neu, EGF, and TNF-A in breast cancer [J]. Cancer Res , 2013 , 73 ( 9 ): 2884 - 2896 .
MIKSE O R , BLAKE D C , JONES N R , et al . FOXO3 encodes a carcinogen-activated transcription factor frequently deleted in early-stage lung adenocarcinoma [J]. Cancer Res , 2010 , 70 ( 15 ): 6205 - 6215 .
YU Z , JU Y , LIU H . Antilung cancer effect of glucosamine by suppressing the phosphorylation of FOXO [J]. Mol Med Rep , 2017 , 16 ( 3 ): 3395 - 3400 .
CARBAJO-PESCADOR S , MAURIZ J L , GARCÍA-PALOMO A , et al . FoxO proteins: regulation and molecular targets in liver cancer [J]. Curr Med Chem , 2014 , 21 ( 10 ): 1231 - 1246 .
杨明建 , 于振涛 . FOXO的调控与肿瘤治疗关系的研究进展 [J]. 中国肿瘤临床 , 2015 , 42 ( 18 ): 926 - 929 .
LIU H , YIN J , WANG C , et al . FOXO3a mediates the cytotoxic effects of cisplatin in lung cancer cells [J]. Anticancer Drugs , 2014 , 25 ( 8 ): 898 - 907 .
NUMASAKI M , WATANABE M , SUZUKI T , et al . IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis [J]. J Immunol , 2005 , 175 ( 9 ): 6177 - 6189 .
GU K , LI M M , SHEN J , et al . Interleukin-17-induced EMT promotes lung cancer cell migration and invasion via NF- κ B/ZEB1 signal pathway [J]. Am J Cancer Res , 2015 , 5 ( 3 ): 1169 - 1179 .
0
浏览量
18
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621