Effect of Csn-B Combined with Imatinib on Apoptosis of Chronic Myeloid Leukemia Cells through Nur77/Pim-1/Drp1 Pathway
Objective:To investigate the anti-chronic myelogenous leukemia(CML)activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression,and explore the potential role of its signaling pathway.Methods:Firstly,CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B,imatinib,and their combination on the proliferation and migration of K562 cells.Furthermore,the apoptosis rate of K562 cells treated with Csn-B,imatinib,and their combination was detected by flow cytometry.The expression levels of Nur77,Pim-1,Drp1,p-Drp1 S616,Bcl-2 and Bax in K562 cells were detected by Western blot.Finally,the expression levels of reactive oxygen species(ROS)in K562 cells treated with Csn-B,imatinib and their combination were detected by immunofluorescence assay.Results:The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754(P＜0.001).Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells(both P＜0.001),and induce apoptosis(P＜0.001).Csn-B promoted Nur77 expression in K562 cells,and synergistically enhanced imatinib sensitivity when combined with imatinib.Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment(both P＜0.001).Conclusion:Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.
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