First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, Shandong, People's Republic of China.
Department of Oncology, Affilited Hospital of Weifang Medical University, Weifang, 261031, Shandong, People's Republic of China.
BMC Complement Altern Med. 2019 Mar 25;19(1):75. doi: 10.1186/s12906-019-2471-2.
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.
(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.
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.
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.
伊马替尼的引入彻底改变了慢性髓系白血病（CML）的治疗方法，显著延长了患者的生存时间。然而，目前伊马替尼耐药是 CML 的一个临床问题。找到抑制伊马替尼耐药的策略非常重要。
（1）我们鉴定了靛玉红及其衍生物，并预测了其潜在的靶点；（2）从基因表达数据库（GEO）下载基因芯片 GSE2810 的数据，并进行 GEO2R 分析，以获得差异表达基因（DEGs）；（3）构建潜在靶点和 DEGs 的 P-P 网络，以探索作用机制并验证分子对接的结果。
我们共鉴定出 42 种小分子化合物，其中 15 种影响 11 个潜在靶点，表明有抑制伊马替尼耐药的潜力；分子对接的结果验证了这些结果。通过分析 DEGs，鉴定出 6 个伊马替尼耐药的生物标志物。
这 15 种小分子化合物通过细胞因子-细胞因子受体信号通路、JAK-STAT 通路和 NF-KB 信号通路抑制伊马替尼耐药。靛玉红及其衍生物可能是对抗伊马替尼耐药的新药。
