
浏览全部资源
扫码关注微信
中国中医科学院 广安门医院,北京 100053
[第一作者] 郑琦,博士,助理研究员,从事中医药防治肿瘤的基础研究,E-mail:fiona19880607@sina.cn
*侯炜,硕士,主任医师,博士生导师,从事中医药防治肿瘤方面的临床和基础研究,E-mail:houwei1964@163.com
收稿日期:2019-05-05,
网络出版日期:2019-09-12,
纸质出版日期:2020-04-05
移动端阅览
郑琦, 侯炜. 基于网络药理学探讨黄连-吴茱萸治疗胃癌的作用机制[J]. 中国实验方剂学杂志, 2020,26(7):204-210.
Qi ZHENG, Wei HOU. Molecular Mechanism of Coptidis Rhizoma-Euodiae Fructus for Gastric Cancer Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(7): 204-210.
郑琦, 侯炜. 基于网络药理学探讨黄连-吴茱萸治疗胃癌的作用机制[J]. 中国实验方剂学杂志, 2020,26(7):204-210. DOI: 10.13422/j.cnki.syfjx.20200122.
Qi ZHENG, Wei HOU. Molecular Mechanism of Coptidis Rhizoma-Euodiae Fructus for Gastric Cancer Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(7): 204-210. DOI: 10.13422/j.cnki.syfjx.20200122.
目的:
2
筛选黄连-吴茱萸配伍对胃癌治疗的主要活性成分,预测两者共同活性成分的作用靶点,建立药物活性成分-靶基因网络,进一步探讨药对黄连-吴茱萸对胃癌治疗的潜在作用机制。
方法:
2
采用中药系统药理学技术平台(TCMSP),筛选黄连-吴茱萸的潜在活性化学物质,借助基因组注释(Genecards)数据库平台,预测和筛选胃癌的作用靶点,采用Cytoscape(3.7.1)软件,构建“药物-活性化学物质-疾病-作用靶点”网络图,借助String数据库平台构建蛋白质相互作用网络。最后利用Bioconductor平台和R语言进行基因本体(GO)富集分析和基因相互作用(KEGG)通路分析。
结果:
2
通过筛选,得到黄连的潜在活性成分14个,吴茱萸的潜在活性成分15个,共涉及与胃癌相关作用靶点127个。黄连-吴茱萸-胃癌共同靶点33个,主要通过调控PTGS2,PTGS1,AR,RXRA,NOS2等靶基因及细胞凋亡,p53信号通路,白细胞介素(IL)-17信号通路等发挥对胃癌的治疗作用。
结论:
2
黄连-吴茱萸对胃癌的治疗作用体现了中药多成分-多靶点的特点,阐明了药对黄连-吴茱萸对胃癌治疗的作用机制与物质基础的科学内涵。
Objective:
2
To identify the main active components of Coptidis Rhizoma and Euodiae Fructus for the treatment of gastric cancer
predict the targets of the common active components in these two herbs
establish the network of active drug components-target genes
and further explore the potential mechanism and effect of Coptidis Rhizoma-Euodiae Fructus for the treatment of gastric cancer.
Method:
2
The active components of Coptidis Rhizoma-Euodiae Fructus were screened by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP)
gastric cancer targets were predicted and screened by Genecard database platform
" drug-active ingredient-disease-targets" networks were built by Cytoscape (3.7.1) software
and protein interaction networks were built by String database platform. Finally
Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Bioconductor platform and R language.
Result:
2
The 14 potential active components of Coptidis Rhizoma and 15 potential active components of Euodiae Fructus were obtained
involving 127 targets related to gastric cancer. There were 33 common targets for Coptidis Rhizoma-Euodiae Fructus-gastric cancer
which played a therapeutic role in gastric cancer mainly by regulating target genes such as PTGS2
PTGS1
AR
RXRA and NOS2
as well as cell apoptosis
p53 signaling pathway and interleukin (IL)-17 signaling pathway.
Conclusion:
2
The therapeutic mechanism of Coptidis Rhizoma-Euodiae Fructus reflects the multi-component
multi-target and multi-pathway characteristics of traditional Chinese medicines and provides the scientific basis for further study and the material basis of Coptidis Rhizoma-Euodiae Fructus against gastric cancer.
陈金东 . 中国各类癌症的发病率和死亡率现状及发展趋势 [J]. 遵义医学院学报 , 2018 , 41 ( 6 ): 653 - 662 .
白慧霞 . 中国胃癌发病率及死亡率研究进展 [J]. 临床医药文献电子杂志 , 2019 , 6 ( 7 ): 192 .
孙洁 , 严广华 . 黄连化学成分及有效成分药理活性的研究进展 [J]. 中国继续医学教育 , 2018 , 10 ( 8 ): 140 - 143 .
冯苗苗 , 王幼平 . 吴茱萸碱在抗炎作用中的研究进展 [J]. 中医临床研究 , 2017 , 9 ( 10 ): 127 - 130 .
赵平 , 许浚 , 张铁军 , 等 . “病-证-方-药”结合探析左金丸配伍的科学内涵 [J]. 中国中药杂志 , 2011 , 36 ( 23 ): 3380 - 3385 .
孙梦瑶 , 王丹丹 , 吴秋雪 , 等 . 左金丸对胃癌耐药细胞SGC-7901/DDP增殖和糖酵解的抑制作用 [J]. 上海中医药大学学报 , 2019 , 33 ( 1 ): 71 - 75 .
张彦博 , 李琦 , 刘艳娜 , 等 . 左金丸通过Wnt/ β -catenin信号通路对幽门螺杆菌感染的人胃癌细胞转移的影响 [J]. 上海中医药大学学报 , 2015 , 29 ( 2 ): 44-47,52 .
叶乃菁 , 刘宣 , 李琦 . 左金丸及其活性成分抗胃癌的实验研究进展 [J]. 中华中医药杂志 , 2014 , 29 ( 4 ): 1162 - 1164 .
T T LUO , Y LU , S K YAN , et al . Network pharmacology in research of chinese medicine formula: methodology, application and prospective [J]. Chin J Integr Med , 2019 , doi: 10.1007/s11655-019-3064-0 http://dx.doi.org/10.1007/s11655-019-3064-0 .
J RU , P LI , J WANG , et al . TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminform , 2014 , doi: 10.1186/1758-2946-6-13 http://dx.doi.org/10.1186/1758-2946-6-13 .
S FISHILEVICH , S ZIMMERMAN , A KOHN , et al . Genic insights from integrated human proteomics in GeneCards [J]. Database (Oxford) , 2016 , doi: 10.1093/database/baw030 http://dx.doi.org/10.1093/database/baw030 .
D SZKLARCZYK , A FRANCESCHINI , S WYDER , et al . STRING v10: protein-protein interaction networks, integrated over the tree of life [J]. Nucleic Acids Res , 2015 , doi: 10.1093/nar/gku1003 http://dx.doi.org/10.1093/nar/gku1003 .
周晟 , 陈澈 , 孟庆刚 . 黄连吴茱萸药对配伍结构及应用规律 [J]. 中医杂志 , 2017 , 58 ( 19 ): 1646 - 1649 .
许燕妮 , 吴江峰 , 丁舸 , 等 . 谈黄连、吴茱萸药对在方剂配伍中的意义 [J]. 光明中医 , 2018 , 33 ( 14 ): 2003 - 2004 .
S T CHOU , C Y HSIANG , H Y LO , et al . Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice [J]. BMC Complement Altern Med , 2017 , 17 ( 1 ): 121 .
A PANDEY , K VISHNOI , S MAHATA , et al . Berberine and curcumin target survivin and STAT3 in gastric cancer cells and synergize actions of standard chemotherapeutic 5-fluorouracil [J]. Nutr Cancer , 2015 , 67 ( 8 ): 1293 - 1304 .
J WANG , S YANG , X CAI , et al . Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer [J]. Oncotarget , 2016 , 7 ( 46 ): 76076 - 76086 .
V PONGKITTIPHAN , W CHAVASIRI , R SUPABPHOL . Antioxidant effect of berberine and its phenolic derivatives against human fibrosarcoma cells [J]. Asian Pac J Cancer Prev , 2015 , 16 ( 13 ): 5371 - 5376 .
D CHAKRAVARTHY , A R MUÑOZ , A SU , et al . Palmatine suppresses glutamine-mediated interaction between pancreatic cancer and stellate cells through simultaneous inhibition of survivin and COL1A1 [J]. Cancer Lett , 2018 , doi: 10.1016/j.canlet.2018.01.057 http://dx.doi.org/10.1016/j.canlet.2018.01.057 .
L L ZHANG , L N MA , D YAN , et al . Dynamic monitoring of the cytotoxic effects of protoberberine alkaloids from Rhizoma Coptidis on HepG2 cells using the xCELLigence system [J]. Chin J Nat Med , 2014 , 12 ( 6 ): 428 - 435 .
H G HAMBRIGHT , I S BATTH , J XIE , et al . Palmatine inhibits growth and invasion in prostate cancer cell: Potential role for rpS6/NF κ B/FLIP [J]. Mol Carcinog , 2015 , 54 ( 10 ): 1227 - 1234 .
J WU , Q XIAO , N ZHANG , et al . Palmatine hydrochloride mediated photodynamic inactivation of breast cancer MCF-7 cells: effectiveness and mechanism of action [J]. Photodiagnosis Photodyn Ther , 2016 , doi: 10.1016/j.pdpdt.2016.07.006 http://dx.doi.org/10.1016/j.pdpdt.2016.07.006 .
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 .
H S SHANG , H F LU , C H LEE , et al . Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells [J]. Environ Toxicol , 2018 , 33 ( 11 ): 1168 - 1181 .
K A MANU , M K SHANMUGAM , L RAMACHANDRAN , et al . Isorhamnetin augments the anti-tumor effect of capecitabine through the negative regulation of NF- κ B signaling cascade in gastric cancer [J]. Cancer Lett , 2015 , 363 ( 1 ): 28 - 36 .
L RAMACHANDRAN , K A MANU , M K SHANMUGAM , et al . Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor γ activation pathway in gastric cancer [J]. J Biol Chem , 2012 , 287 ( 45 ): 38028 - 38040 .
E J SHIN , H K CHOI , M J SUNG , et al . Anti-tumour effects of beta-sitosterol are mediated by AMPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells and xenograft mouse models [J]. Biochem Pharmacol , 2018 , doi: 10.1016/j.bcp.2018.03.010 http://dx.doi.org/10.1016/j.bcp.2018.03.010 .
Y ZHAO , S K CHANG , G QU , et al . Beta-sitosterol inhibits cell growth and induces apoptosis in SGC-7901 human stomach cancer cells [J]. J Agric Food Chem , 2009 , 57 ( 12 ): 5211 - 5218 .
0
浏览量
17
下载量
3
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621