EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway

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 leukem...

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Veröffentlicht in:Tumor biology 2016-05, Vol.37 (5), p.5919-5923
Hauptverfasser: Zhang, Hao, Gu, Huizi, Li, Limei, Ren, Yuan, Zhang, Lijun
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container_title Tumor biology
container_volume 37
creator Zhang, Hao
Gu, Huizi
Li, Limei
Ren, Yuan
Zhang, Lijun
description 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  
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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  &lt; 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. 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Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Hao</au><au>Gu, Huizi</au><au>Li, Limei</au><au>Ren, Yuan</au><au>Zhang, Lijun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>37</volume><issue>5</issue><spage>5919</spage><epage>5923</epage><pages>5919-5923</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><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  &lt; 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.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26592252</pmid><doi>10.1007/s13277-015-4463-2</doi><tpages>5</tpages></addata></record>
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source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Arsenicals - pharmacology
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Line, Tumor
Drug Resistance, Neoplasm - drug effects
Enhancer of Zeste Homolog 2 Protein - genetics
Enhancer of Zeste Homolog 2 Protein - metabolism
Flow cytometry
Gene Expression
Gene Knockdown Techniques
Glycogen Synthase Kinase 3 beta - metabolism
HL-60 Cells
Humans
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - metabolism
Original Article
Oxides - pharmacology
Phosphorylation
Studies
Wnt Signaling Pathway - drug effects
title EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway
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