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基于整合药理学方法解析茯苓干预乳腺癌的关键药理途径

Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method.

作者信息

Ma Xiaoran, Wu Jibiao, Liu Cun, Li Jie, Dong Shixia, Zhang Xiaolu, Wang Jia, Liu Lijuan, Zhang Xiaoming, Sun Peng, Zhuang Jing, Sun Changgang

机构信息

College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China.

出版信息

Evid Based Complement Alternat Med. 2020 Oct 9;2020:4931531. doi: 10.1155/2020/4931531. eCollection 2020.

Abstract

OBJECTIVE

Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood.

METHODS

TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results.

RESULTS

In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway.

CONCLUSION

The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

摘要

目的

茯苓,一种天然植物,最近已成为一种有前景的癌症治疗策略。然而,茯苓在乳腺癌中的作用分子机制仍知之甚少。

方法

利用中药系统药理学数据库与分析平台(TCMSP)筛选茯苓中的潜在活性成分。利用基因表达综合数据库(GEO)鉴定差异表达基因。采用网络药理学方法确定与乳腺癌相关的特定途径和关键靶蛋白。最后,通过分子对接验证结果。

结果

在我们的研究中,预测茯苓中发现的15种潜在活性成分有237个靶点。构建了预测靶点与乳腺癌中差异调节基因的相互作用网络。基于构建的网络以及包括网络拓扑、京都基因与基因组百科全书(KEGG)、生存分析和基因集富集分析在内的进一步分析,确定了3个主要节点为关键潜在靶点,这些靶点在过氧化物酶体增殖物激活受体(PPAR)信号通路中显著富集。

结论

结果表明,茯苓的潜在活性成分可能通过对环氧合酶2(PTGS2)、雌激素受体1(ESR1)和原癌基因FOS的协同调节来干扰乳腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfac/7603580/30e246af3700/ECAM2020-4931531.001.jpg

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