Anti-colorectal Cancer Molecular Mechanism of Astragali Radix and Curcumae Rhizoma Based on Network Pharmacology

Fu-yan LIU; De-cai TANG; Xi-ying TAN

doi:10.13422/j.cnki.syfjx.20190827

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Anti-colorectal Cancer Molecular Mechanism of Astragali Radix and Curcumae Rhizoma Based on Network Pharmacology

Data Mining | 更新时间：2021-02-09

- Anti-colorectal Cancer Molecular Mechanism of Astragali Radix and Curcumae Rhizoma Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 13, Pages: 176-185(2019)
- 作者机构：
  
  南京中医药大学　基础医学院，南京　 210046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190827
  CLC： R22; R242; R2-031; R285.5
- Received：13 September 2018，
  
  Published Online：04 January 2019，
  
  Published：05 July 2019
- 稿件说明：
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Fu-yan LIU, De-cai TANG, Xi-ying TAN. Anti-colorectal Cancer Molecular Mechanism of Astragali Radix and Curcumae Rhizoma Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 176-185.
DOI：

Fu-yan LIU, De-cai TANG, Xi-ying TAN. Anti-colorectal Cancer Molecular Mechanism of Astragali Radix and Curcumae Rhizoma Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 176-185. DOI： 10.13422/j.cnki.syfjx.20190827.

摘要

目的：

运用计算机网络药理学技术预测黄芪-莪术药对治疗大肠癌的作用靶点和信号通路，进一步分析其抗大肠癌物质基础和作用机制。

方法：

通过Therapetutic Target Database(TTD)，Drugbank数据库收集大肠癌疾病作用靶点；从中药系统药理学分析平台(TCMSP)获得黄芪、莪术所含中药成分；运用ChemMapper，PharmMapper数据库预测所选中药成分作用的疾病靶点；采用Cytoscape 软件建立“化合物-疾病靶点”网络模型；利用ClueGO插件对靶点进行基因功能(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。

结果：

黄芪-莪术药对活性化合物-大肠癌疾病靶点网络包含56个化合物和54个靶点，关键靶点涉及AMP激活蛋白激酶

(PRKAA1)，前列腺素内过氧化物合酶1(PTGS1)，环氧化酶2(PTGS2)，胸苷酸合成酶(TYMS)，肝羧酯酶1(CES1)，血管内皮生长因子B(VEGFB)，血管内皮生长因子A(VEGFA)，谷胱甘肽S-转移酶P(GSTP1)，丝氨酸羟甲基转移酶(glyA)等；靶点的基因功能偏向于肽基酪氨酸的磷酸化，调节细胞外调节蛋白激酶(ERK)1和ERK2信号串联，内皮细胞凋亡过程的负调节等；重要的KEGG通路涉及癌症通路，Ras信号通路，Rap1信号通路，磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路等。

结论：

黄芪-莪术药对通过抑制肿瘤细胞增殖分化、促进肿瘤细胞凋亡、抗肿瘤新生血管生成以及增强机体免疫的多表型干预的网络模式产生抗大肠癌活性，其作用信号通路与Ras信号通路，Rap1信号通路，PI3K/Akt信号通路最为相关。

Abstract

Objective:

The network pharmacology method was used to predict targets and signaling pathways of the drug pair Astragali Radix and Curcumae Rhizoma in treating colorectal cancer

in order to analyze the effective material basis and action mechanism.

Method:

Disease targets for colorectal cancer were collected through Therapetutic Target Database(TTD)and Drugbank database. Components of Astragali Radix and Curcumae Rhizoma were obtained from the Traditional Chinese Medicine Systems Pharmacology Database

and the Analysis Platform (TCMSP). ChemMapper and PharmMapper database were used to predict the disease targets of effective components. The " compound-disease targets" network model was established by Cytoscape software. The function analysis of gene ontology(GO)and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG)were carried out with ClueGO plug-in.

Result:

The network contained 56 compounds and 54 targets. The crucial targets included 5′-AMP-activated protein kinase catalytic subunit alpha1(PRKAA1)

prostaglandin G/H synthase 1(PTGS1)

prostaglandin G/H synthase 2(PTGS2)

Thymidylate synthase(TYMS)

Carboxylesterase 1(CES1)

vascular endothelial growth factor B(VEGFB)

vascular endothelial growth factor A(VEGFA)

glutathione S-transferase P(GSTP1)

and serine hydroxymethyltransferase 1(glyA). Function about target genes inclined to peptide-tyrosine phosphorylation

extracellular regulated protein kinase(ERK)1 and ERK2 signal series

negative regulation of endothelial cell apoptosis process

et al. Important KEGG Pathways involved pathways in cancer

Ras signaling pathways

Rap1 signaling pathways

and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways.

Conclusion:

The anti-colorectal cancer activities of Astragali Radix and Curcumae Rhizoma were mainly affected by inhibiting cell proliferation and differentiation

promoting tumor cell apoptosis

resisting tumor angiogenesis

and enhancing immunity as phenotype intervention mode in network. The active signaling pathway is most related to Ras signaling pathway

Rap1 signaling pathway and PI3K/Akt signaling pathway.

关键词

Keywords

references

Msph L A T , Bray F , Siegel R L , et al . Global cancer statistics, 2012 [J]. CA Cancer J Clin , 2015 , 65 ( 2 ): 87 - 108 .

陈万青，孙可欣，郑荣寿，等． 2014年中国分地区恶性肿瘤发病和死亡分析 [J]．中国肿瘤， 2018 ， 27 ( 1 )： 1 - 14 ．

曹子丰，唐德才，时晓霞，等．黄芪、莪术配伍联合奥沙利铂对CT26．WT原位移植瘤小鼠中CXCR3、CCR6表达影响 [J]．北京中医药大学学报， 2017 ， 40 ( 6 )： 477 - 482 ．

国家药典委员会．中华人民共和国药典．一部 [M]．北京：中国医药科技出版社， 2015 ： 302 - 303 ．

吴相文．张锡纯使用对药举隅 [J]．河北中医， 2009 ， 31 ( 12 )： 1886 - 1888 ．

Hopkins A L . Network pharmacology: the next paradigm in drug discovery [J]. Nat Chem Biol , 2008 , 4 ( 11 ): 682 - 690 .

LI S , ZHANG B . Traditional Chinese medicine network pharmacology: theory, methodology and application [J]. Chin J Nat Med , 2013 , 11 ( 2 ): 110 - 120 .

XU X , ZHANG W , HUANG C , et al . A novel chemometric method for the prediction of human oral bioavailability [J]. Int J Mol Sci , 2012 , 13 ( 12 ): 6964 - 6982 .

GONG J , CAI C , LIU X , et al . ChemMapper: a versatile web server for exploring pharmacology and chemical structure association based on molecular 3D similarity method [J]. Bioinformatics , 2013 , 29 ( 14 ): 1827 - 1829 .

WANG X , SHEN Y , WANG S , et al . PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database . [J]. Nucleic Acids Res , 2017 , 45 ( W1 ): 356 - 360 .

高云峰，高娜．黄芪生理活性成分及其药理作用研究进展 [J]．新农业， 2017 ( 1 )： 20 - 21 ．

刘洋，杜婧，沈颜红． 10种药用黄芪属植物化学成分及药理作用的研究进展 [J]．中国实验方剂学杂志， 2017 ， 23 ( 18 )： 222 - 234 ．

郭丽娟，张云，丛晓东，等．温郁金主要成分含量测定及指纹图谱研究进展 [J]．中国中医药信息杂志， 2011 ， 18 ( 4 )： 101 - 103 ．

王颖，郭兰萍，黄璐琦，等．姜黄、莪术、郁金的化学成分与药理作用研究进展 [J]．中国药房， 2013 ， 24 ( 35 )： 3338 - 3341 ．

张贵杰，黄克斌．广西莪术化学成分和药理作用研究进展 [J]．广州化工， 2015 ， 43 ( 11 )： 24 - 26 ．

肖智勇，周文霞，张永祥．基于网络药理学的抗肿瘤药物发现策略 [J]．国际药学研究杂志， 2014 ， 41 ( 1 )： 1 - 6 ．

YU H , ZHANG H , DONG M , et al . Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells [J]. Int J Oncol , 2017 , 50 ( 1 ): 161 - 172 .

Larsen A K , Gramont A D , Poindessous V , et al . Functions and clinical implications of autocrine VEGF signaling in colorectal cancer [J]. Curr Colorectal Cancer Rep , 2013 , 9 ( 3 ): 270 - 277 .

Park J J , Seo S M , Kim E J , et al . Berberine inhibits human colon cancer cell migration via AMP-activated protein kinase-mediated downregulation of integrin β1 signaling [J]. Biochem Biophys Res Commun , 2012 , 426 ( 4 ): 461 - 467 .

王子元，王荟，刘坤，等． AMPK-α/NF-κB信号转导通路在大肠癌多药耐药中的作用及白藜芦醇的干预机制 [J]．中华中医药杂志， 2017 ， 32 ( 7 )： 3266 - 3269 ．

Williams C S , Mann M , Dubois R N . The role of cyclooxygenases in inflammation, cancer, and development [J]. Oncogene , 1999 , 18 ( 55 ): 7908 - 7916 .

张翅腾，王毅． COX2-PGE2调节肿瘤的发生和发展机制研究进展 [J]．西南军医， 2018 ， 20 ( 1 )： 50 - 53 ．

Benelli R , Venè R , Ferrari N . Prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), a complex target for colorectal cancer prevention and therapy [J]. Transl Res , 2018 , doi: 10.1016/j.trsl.2018.01.003 http://doi.org/10.1016/j.trsl.2018.01.003 .

王明，李兴德，朱中成． DPYD、TYMS及MTHFR基因表达与直肠癌放化疗敏感性的关系 [J]．现代肿瘤医学， 2015 ， 23 ( 12 )： 1697 - 1700 ．

刘帅兵，缪丽燕．羧酸酯酶1和2基因多态性在药物代谢中的研究进展 [J]．中国临床药学杂志， 2015 ， 24 ( 3 )： 206 - 210 ．

向本旭，刘婷婷，孙芳玲，等． VEGF相关信号通路在血管新生中的研究进展 [J]．中国比较医学杂志， 2015 ， 25 ( 12 )： 81 - 86 ．

WANG A L , LI Y , ZHAO Q , et al . Formononetin inhibits colon carcinoma cell growth and invasion by microRNA149mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways [J]. Mol Med Rep , 2018 , 17 ( 6 ): 7721 - 7729 .

WANG J , LI X M , BAI Z , et al . Curcumol induces cell cycle arrest in colon cancer cells via reactive oxygen species and Akt/GSK3β/cyclin D1 pathway [J]. J Ethnopharmacol , 2017 , doi: 10.1016/j.jep.2017.06.037 http://doi.org/10.1016/j.jep.2017.06.037 .

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