title: Neutrophil elastase and its therapeutic effect on leukemia cells.
abstract: Neutrophil elastase (NE) is an early myeloid-specific serine protease, which is predominantly produced by promyelocytes. A previous study demonstrated that NE has an important role in the development of acute promyelocytic leukemia (APL). The process of APL was shown to be accelerated in animals that expressed abundant NE, whereas NE‑deficient mice were protected from APL development; thus suggesting an important role for NE in the development of APL. The present study aimed to investigate the effects and possible mechanisms of NE. Up- and downregulation of NE in various leukemia cell lines was conducted in order to explore its significance in the occurrence and procession of leukemia, with the aim of identifying novel targeted therapeutic drugs for the treatment of leukemia. NE was overexpressed in cells following infection with an adenovirus, and Cell Counting kit‑8 and flow cytometry results demonstrated that cell proliferation was promoted, and cell apoptosis was inhibited, as compared with the untreated cells. NE was downregulated in the cells by both RNA interference and treatment with GW311616A, a specific inhibitor of NE, following which cell growth was shown to be inhibited and apoptosis was induced. These results suggested that NE may promote the development of APL, therefore, NE may be a therapeutic target and its inhibitor GW311616A may be a potential therapeutic drug for leukemia. Furthermore, the apoptosis‑associated protein B‑cell lymphoma 2 (Bcl‑2)‑associated X protein was significantly increased, whereas Bcl‑2 was markedly decreased in the cells with downregulated NE. Further experiments revealed that the probable apoptosis‑associated signaling pathway was the phosphoinositide 3‑kinase/AKT pathway. The present study is the first, to the best of our knowledge, to demonstrate that GW311616A, a specific NE inhibitor, may act as a potential targeted drug for leukemia, which may have a profound impact on the future of leukemia-targeted therapy.
authors.affiliation: Central Laboratory of Yong‑Chuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
authors.forename: Kai-Ling
authors.initials: KL
authors.lastname: Jiang
authors.affiliation: Central Laboratory of Yong‑Chuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
authors.forename: Peng-Peng
authors.initials: PP
authors.lastname: Ma
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Central Laboratory of Yong‑Chuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
authors.forename: Bei-Zhong
authors.initials: BZ
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C119405:GW 311616; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019272:Leukocyte Elastase