title: EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway.
abstract: In this study, we examined the mechanisms associated with EZH2 mediation of apoptosis and chemoresistance to arsenic trioxide (ATO) in acute myeloid leukemia (AML) cell lines through the Wnt/β-catenin signaling pathway. The induction of spontaneous apoptosis observed in multiple EZH2-silenced leukemic cell lines was assessed by flow cytometry, and levels of Wnt/β-catenin-related expression were determined by western blot analysis. In comparison with AML control cells, EZH2-knockdown cells exhibited increased apoptosis and significant downregulation of β-catenin expression, as well as decreases in GSK-3β phosphorylation and β-catenin activation (p < 0.05 for all measurements). Additionally, EZH2 knockdown sensitized AML cells to induced cell death following administration of chemotherapeutic ATO. Our results suggested that EZH2 in leukemic cell lines might inhibit ATO-induced apoptosis and that EZH2 may be a potential therapeutic target in AML patients undergoing ATO treatment. Our findings provide new insights into the role of ATO and EZH2 in regulating AML progression.
authors.affiliation: Department of Hematology, The First Hospital of China Medical University, Shenyang, China, 110001.|Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, The Second Hospital of Dalian Medical University, Dalian, China, 116027.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Hospital of Dalian Medical University, Dalian, China, 116027.
authors.forename: Huizi
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Hematology, The People's Hospital of Liaoning Province, Shenyang, China, 110016.
authors.forename: Limei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Hospital of China Medical University, Shenyang, China, 110001.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Hematology, The First Hospital of China Medical University, Shenyang, China, 110001. 13514201170@126.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D010766:Phosphorylation; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000071221:Enhancer of Zeste Homolog 2 Protein; D000071679:Glycogen Synthase Kinase 3 beta; D000077237:Arsenic Trioxide
keywords: ATO; Acute myeloid leukemia; EZH2; Wnt/β-catenin