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蟾毒灵对乳腺癌MCF-7细胞潜在作用机制的计算机模拟分析

In silico analysis of the potential mechanism of telocinobufagin on breast cancer MCF-7 cells.

作者信息

Dang Yi-Wu, Lin Peng, Liu Li-Min, He Rong-Quan, Zhang Li-Jie, Peng Zhi-Gang, Li Xiao-Jiao, Chen Gang

机构信息

Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, PR China.

The Ultrasonics Division of Radiology Department, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, PR China.

出版信息

Pathol Res Pract. 2018 May;214(5):631-643. doi: 10.1016/j.prp.2018.03.029. Epub 2018 Apr 5.

DOI:10.1016/j.prp.2018.03.029
PMID:29656985
Abstract

BACKGROUNDS AND AIMS

The extractives from a ChanSu, traditional Chinese medicine, have been discovered to possess anti-inflammatory and tumor-suppressing abilities. However, the molecular mechanism of telocinobufagin, a compound extracted from ChanSu, on breast cancer cells has not been clarified. The aim of this study is to investigate the underlying mechanism of telocinobufagin on breast cancer cells.

METHODS AND MATERIALS

The differentially expressed genes after telocinobufagin treatment on breast cancer cells were searched and downloaded from Gene Expression Omnibus (GEO), ArrayExpress and literatures. Bioinformatics tools were applied to further explore the potential mechanism of telocinobufagin in breast cancer using the Kyoto Encyclopedia of genes and genomes (KEGG) pathway, Gene ontology (GO) enrichment, panther, and protein-protein interaction analyses. To better comprehend the role of telocinobufagin in breast cancer, we also queried the Connectivity Map using the gene expression profiles of telocinobufagin treatment.

RESULTS

One GEO accession (GSE85871) provided 1251 differentially expressed genes after telocinobufagin treatment on MCF-7 cells. The pathway of neuroactive ligand-receptor interaction, cell adhesion molecules (CAMs), intestinal immune network for IgA production, hematopoietic cell lineage and calcium signaling pathway were the key pathways from KEGG analysis. IGF1 and KSR1, owning to higher protein levels in breast cancer tissues, IGF1 and KSR1 could be the hub genes related to telocinobufagin treatment. It was indicated that the molecular mechanism of telocinobufagin resembled that of fenspiride.

CONCLUSIONS

Telocinobufagin might regulate neuroactive ligand-receptor interaction pathway to exert its influences in breast cancer MCF-7 cells, and its molecular mechanism might share some similarities with fenspiride. This study only presented a comprehensive picture of the role of telocinobufagin in breast cancer MCF-7 cells using big data. However, more thorough and deeper researches are required to add to the validity of this study.

摘要

背景与目的

已发现中药蟾酥提取物具有抗炎和抑癌能力。然而,从蟾酥中提取的化合物远华蟾毒精对乳腺癌细胞的分子机制尚未阐明。本研究旨在探讨远华蟾毒精对乳腺癌细胞的潜在作用机制。

方法与材料

从基因表达综合数据库(GEO)、ArrayExpress数据库及文献中搜索并下载远华蟾毒精处理乳腺癌细胞后差异表达的基因。运用生物信息学工具,通过京都基因与基因组百科全书(KEGG)通路、基因本体(GO)富集分析、泛素分析及蛋白质-蛋白质相互作用分析,进一步探究远华蟾毒精在乳腺癌中的潜在作用机制。为更好地理解远华蟾毒精在乳腺癌中的作用,我们还利用远华蟾毒精处理的基因表达谱查询了连接图谱。

结果

一个GEO登录号(GSE85871)提供了远华蟾毒精处理MCF-7细胞后1251个差异表达基因。神经活性配体-受体相互作用、细胞黏附分子(CAMs)、IgA产生的肠道免疫网络、造血细胞谱系及钙信号通路是KEGG分析中的关键通路。由于在乳腺癌组织中蛋白水平较高,胰岛素样生长因子1(IGF1)和激酶抑制蛋白1(KSR1)可能是与远华蟾毒精处理相关的枢纽基因。结果表明,远华蟾毒精的分子机制与非那吡啶相似。

结论

远华蟾毒精可能通过调节神经活性配体-受体相互作用通路在乳腺癌MCF-7细胞中发挥作用,其分子机制可能与非那吡啶有一些相似之处。本研究仅利用大数据全面呈现了远华蟾毒精在乳腺癌MCF-7细胞中的作用。然而,需要更深入和全面的研究来增强本研究的有效性。

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