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Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy

BACKGROUND: The introduction of imatinib revolutionized the treatment of chronic myeloid leukaemia (CML), substantially extending patient survival. However, imatinib resistance is currently a clinical problem for CML. It is very importantto find a strategy to inhibit imatinib resistance. METHODS: (1...

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Autores principales: Li, Huayao, Liu, Lijuan, Zhuang, Jing, Liu, Cun, Zhou, Chao, Yang, Jing, Gao, Chundi, Liu, Gongxi, Sun, Changgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434895/
https://www.ncbi.nlm.nih.gov/pubmed/30909944
http://dx.doi.org/10.1186/s12906-019-2471-2
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author Li, Huayao
Liu, Lijuan
Zhuang, Jing
Liu, Cun
Zhou, Chao
Yang, Jing
Gao, Chundi
Liu, Gongxi
Sun, Changgang
author_facet Li, Huayao
Liu, Lijuan
Zhuang, Jing
Liu, Cun
Zhou, Chao
Yang, Jing
Gao, Chundi
Liu, Gongxi
Sun, Changgang
author_sort Li, Huayao
collection PubMed
description BACKGROUND: The introduction of imatinib revolutionized the treatment of chronic myeloid leukaemia (CML), substantially extending patient survival. However, imatinib resistance is currently a clinical problem for CML. It is very importantto find a strategy to inhibit imatinib resistance. METHODS: (1) We Identified indirubin and its derivatives and predicted its putative targets; (2) We downloaded data of the gene chip GSE2810 from the Gene Expression Omnibus (GEO) database and performed GEO2R analysis to obtain differentially expressed genes (DEGs); and (3) we constructed a P-P network of putative targets and DEGs to explore the mechanisms of action and to verify the results of molecular docking. RESULT: We Identified a total of 42 small-molecule compounds, of which 15 affected 11 putative targets, indicating the potential to inhibit imatinib resistance; the results of molecular docking verified these results. Six biomarkers of imatinib resistance were characterised by analysing DEGs. CONCLUSION: The 15 small molecule compounds inhibited imatinib resistance through the cytokine-cytokine receptor signalling pathway, the JAK-stat pathway, and the NF-KB signalling pathway. Indirubin and its derivatives may be new drugsthat can combat imatinib resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-019-2471-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-64348952019-04-08 Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy Li, Huayao Liu, Lijuan Zhuang, Jing Liu, Cun Zhou, Chao Yang, Jing Gao, Chundi Liu, Gongxi Sun, Changgang BMC Complement Altern Med Research Article BACKGROUND: The introduction of imatinib revolutionized the treatment of chronic myeloid leukaemia (CML), substantially extending patient survival. However, imatinib resistance is currently a clinical problem for CML. It is very importantto find a strategy to inhibit imatinib resistance. METHODS: (1) We Identified indirubin and its derivatives and predicted its putative targets; (2) We downloaded data of the gene chip GSE2810 from the Gene Expression Omnibus (GEO) database and performed GEO2R analysis to obtain differentially expressed genes (DEGs); and (3) we constructed a P-P network of putative targets and DEGs to explore the mechanisms of action and to verify the results of molecular docking. RESULT: We Identified a total of 42 small-molecule compounds, of which 15 affected 11 putative targets, indicating the potential to inhibit imatinib resistance; the results of molecular docking verified these results. Six biomarkers of imatinib resistance were characterised by analysing DEGs. CONCLUSION: The 15 small molecule compounds inhibited imatinib resistance through the cytokine-cytokine receptor signalling pathway, the JAK-stat pathway, and the NF-KB signalling pathway. Indirubin and its derivatives may be new drugsthat can combat imatinib resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-019-2471-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-25 /pmc/articles/PMC6434895/ /pubmed/30909944 http://dx.doi.org/10.1186/s12906-019-2471-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Li, Huayao
Liu, Lijuan
Zhuang, Jing
Liu, Cun
Zhou, Chao
Yang, Jing
Gao, Chundi
Liu, Gongxi
Sun, Changgang
Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
title Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
title_full Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
title_fullStr Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
title_full_unstemmed Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
title_short Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
title_sort deciphering the mechanism of indirubin and its derivatives in the inhibition of imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434895/
https://www.ncbi.nlm.nih.gov/pubmed/30909944
http://dx.doi.org/10.1186/s12906-019-2471-2
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