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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

Author:
Li, Huayao, Liu, Lijuan, Zhuang, Jing, Liu, Cun, Zhou, Chao, Yang, Jing, Gao, Chundi, Liu, Gongxi, Sun, Changgang
Source:
BMC complementary and alternative medicine 2019 v.19 no.1 pp. 75
ISSN:
1472-6882
Subject:
DNA microarrays, alternative medicine, biomarkers, computer simulation, databases, drugs, gene expression, genes, mechanism of action, myeloid leukemia, patients, signal transduction, transcription factor NF-kappa B
Abstract:
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.
Agid:
6349238