The Pharmacological Inhibition Of Erk5 Enhances Apoptosis In Acute Myeloid Leukemia Cells

INTERNATIONAL JOURNAL OF STEM CELLS(2018)

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摘要
Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Extracellular signal-regulated kinase 5(ERK5) plays a novel role in chemoresistance in some cancer cells and this pathway is a central mediator of cell survival and apoptotic regulation. The aim of this study was to investigate the effect of ERK5 inhibitor,XMD8-92, on proliferation and apoptosis in AML cell lines. bindings showed that. XMD8-92 inhibited the activation of ERK5 by G-CSF and decreased the expression of c-Myc and Cyclin D1. The treatment of XMD8-92 reduced the phosphorylation of ERK5 leading to a distinct inhibition of cell proliferation and increased apoptosis in Kasumi-1 and HL-60 cells. Taken together, our study suggests that the inhibition of ERK5 by XMD8-92 can trigger apoptosis and inhibit proliferation in, AMLs. Therefore, the inhibition of ERK5 may be an effective adjuvant in AML chemotherapy.
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关键词
ERK5, XMD8-92, Cell cycle, Apoptosis, Acute myeloid leukemia
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