基于网络药理学探讨抵当汤治疗膀胱癌的作用机制

沈炀; 芦倩; 张东健; 汤井源; 朱辰; 朱清毅; 卢子杰; 袁琳

doi:10.13422/j.cnki.syfjx.20201423

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基于网络药理学探讨抵当汤治疗膀胱癌的作用机制

数据挖掘 | 更新时间：2020-09-09

- 基于网络药理学探讨抵当汤治疗膀胱癌的作用机制
- Mechanism of Didangtang in Treatment of Bladder Cancer Based on Network Pharmacology
- 中国实验方剂学杂志 2020年26卷第14期页码：200-207
- 作者机构：
  
  南京中医药大学附属医院，江苏省中医院，南京 210000
- 作者简介：
  
  沈炀，在读硕士，从事中西医结合泌尿系肿瘤研究，E-mail：dryang9483@126.com
  袁琳，博士，副教授，博士生导师，从事中西医结合泌尿系肿瘤研究，Tel：025-86617141，E-mail：yuanlin47@163.com
- 基金信息：
  
  江苏省中医药科技发展计划项目(YB201920);南京市科技计划项目(201605009);江苏省中医院创新发展基金项目(Y2019CX11)
- DOI：10.13422/j.cnki.syfjx.20201423
  中图分类号： R22;R242;R2-031;R285.5
- 纸质出版日期：2020-07-20，
  
  网络出版日期：2020-05-06，
- 稿件说明：
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沈炀,芦倩,张东健等.基于网络药理学探讨抵当汤治疗膀胱癌的作用机制[J].中国实验方剂学杂志,2020,26(14):200-207.

SHEN Yang,LU Qian,ZHANG Dong-jian,et al.Mechanism of Didangtang in Treatment of Bladder Cancer Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):200-207.
沈炀,芦倩,张东健等.基于网络药理学探讨抵当汤治疗膀胱癌的作用机制[J].中国实验方剂学杂志,2020,26(14):200-207. DOI： 10.13422/j.cnki.syfjx.20201423.

SHEN Yang,LU Qian,ZHANG Dong-jian,et al.Mechanism of Didangtang in Treatment of Bladder Cancer Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):200-207. DOI： 10.13422/j.cnki.syfjx.20201423.

摘要

目的

探讨抵当汤治疗膀胱癌的作用靶点及可能作用机制。

方法

基于多个中药与疾病数据库，运用网络药理学筛选潜在作用靶点，分析潜在靶点的生物学功能，构建“中药-靶点-通路-疾病”关系网络。并运用生物信息学方法在人群、基因数据库，探讨核心靶点的在组织中差异表达，人群中的分布以及与预后的相关性。采用体外实验验证抵当汤的作用功能，并检测抵当汤对候选靶点的作用机制。

结果

本研究共筛选出21个核心靶点，16条通路，构建了抵当汤治疗膀胱癌的作用网络。检测出6个靶点：钙黏蛋白1（CDH1），环磷腺苷结合蛋白1（CREB1），菌落刺激因子2（CSF2），AP-1转录因子（JUN），基质金属肽酶2（MMP2）和前列腺素-内过氧化物合成酶（PTGS2）在膀胱癌组织中均存在差异表达（

0.05），其中JUN与MMP2在人群中也存在差异分布（

0.05）。同时，JUN的表达水平与膀胱癌患者的预后相关（

0.05）。细胞实验发现抵当汤可抑制膀胱癌细胞的增殖，同时可降低候选靶点JUN的表达（

0.01）。

结论

抵当汤治疗膀胱癌存在多靶点、多通路的特点。其中已初步证实抵当汤可影响靶点JUN的表达并抑制膀胱癌的增殖，为进一步机制研究奠定良好基础。

Abstract

Objective

To investigate the targets and possible mechanism of Didangtang in the treatment of bladder cancer.

Method

Based on multiple traditional Chinese medicine and disease databases

the network pharmacology was used to screen potential targets

analyze the biological functions of potential targets

and construct a network of "Chinese medicine-target-path-disease". Bioinformatics analysis was applied in population and gene databases

in order to explore the differential expressions of core targets in tissues

distribution in the population and the correlation with prognosis. The

in vitro

experiment was used to verify the biological function of Didangtang. The underlying mechanism of Didangtang on the candidate target was detected.

Result

A total of 21 core target genes and 16 highly enriched pathways were screened out. A functional network of Didangtang was constructed systematically. At the same time

six targets

namely cadherin 1 (CDH1)

CAMP responsive element binding protein 1 (CREB1)

colony stimulating factor 2 (CSF2)

AP-1 transcription factor (JUN)

matrix metalloproteinase 2 (MMP2)

and prostaglandin-endoperoxide synthase (PTGS2)

were differentially expressed in bladder cancer tissues (

0.05). Furthermore

JUN and MMP2 were also differentially distributed in population (

0.05). At the same time

the expression level of JUN was correlated with the prognosis of patients with bladder cancer (

0.05). The

in vitro

experiment revealed that Didangtang inhibited the proliferation of bladder cancer cells and decreased the expression of candidate target JUN (

0.01).

Conclusion

Didangtang has the characteristics of multiple targets and multiple pathways in treatment of bladder cancer. It is initially confirmed that Didangtang can affect the expression of target JUN and inhibit the proliferation of bladder cancer

which lays a good foundation for further studies on mechanism.

关键词

抵当汤膀胱癌网络药理学靶点

Keywords

Didangtangbladder cancernetwork pharmacologytarget gene

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