EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway
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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.
KeywordsAcute myeloid leukemia ATO EZH2 Wnt/β-catenin
This study was funded by the National Natural Science Foundation of China (No. 81402384) and the Natural Science Foundation of Liaoning Province (201202288).
Hao Zhang and Yuan Ren carried out the molecular genetic studies and drafted the manuscript. Limei Li and Lijun Zhang participated in the design of the study, and Huizi Gu performed the statistical analysis. Lijun Zhang conceived of the study, participated in its design and coordination, and helped draft the manuscript. All authors read and approved the final manuscript.
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Conflicts of interest
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