Neutrophil elastase enhances the proliferation and decreases apoptosis of leukemia cells via activation of PI3K/Akt signaling

Neutrophil elastase (NE) is a neutrophil-derived serine proteinase with specificity for a broad range of substrates. NE has been reported to be associated with the pathogenesis of several conditions, particularly that of pulmonary diseases. Previous studies have shown that NE can cleave the pro-myelocyte - retinoic acid receptor-alpha chimeric protein and is important for the development of acute pro-myelocytic leukemia. To further elucidate the role of NE in acute pro-myelocytic leukemia, the present study successfully constructed a lentiviral vector containing the NE gene (LV5-NE), which was transfected into NB4 acute pro-myelocytic leukemia cells. The effects of NE overexpression in NB4 cells were detected using a Cell-Counting Kit-8 assay, flow cytometry and western blot analysis. The results showed that NE significantly promoted the proliferation of NB4 cells, inhibited cell apoptosis and apoptotic signaling, and led the activation of Akt. In an additional experiment, a vector expressing small hairpin RNA targeting NE was constructed to assess the effects of NE knockdown in U937 cells. Western blot analysis revealed that apoptotic signaling was increased, while Akt activation was decreased following silencing of NE. The results of the present study may indicate that NE activates the phosphoinositide-3 kinase/Akt signaling pathway in leukemia cells to inhibit apoptosis and enhance cell proliferation, and may therefore represent a molecular target for the treatment of pro-myelocytic leukemia.