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Salinomycin Inhibits Acute Promyelocytic Leukemia Cells Proliferation and Induces Differentiation
Zhao Yi1,2, Liu Beizhong1,2, Yao Shifei1,2, Liu Lu2, Chen Min1,2, Li Lianwen1, Xiao Chunlan1,2, Shan Zhiling2, Gan Liugen1,2, Xu Ting1,2, Zhong Liang2*
1Central Laboratory, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing 402160, China; 2Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, China
Abstract: This study is aimed to investigate the effects of salinomycin (SAL) on cell proliferation and differentiation in acute promyelocytic leukemia cell line NB4 and its potential mechanisms. In this study， cell proliferation was determined by cell counting kit-8 (CCK-8) assay， and cell morphological changes was evaluated by performing Wright Giemsa staining. The expression of cell surface differentiation marker CD11b was detected by flow cytometry. The protein levels of CD11b， C/EBPβ， β-catenin， C-myc and Cyclin D1 were detected by Western blot. The results indicated that SAL significantly inhibited cell proliferation， cells displayed morphological features of differentiation after treated with SAL for 72 h. SAL treatment significantly increased the percentage of CD11b-positive cells and protein levels of CD11b and C/EBPβ in a dose-dependent manner. In addition， SAL decreased the protein levels of β-catenin， C-myc and Cyclin D1. This study also investigated the effect of combined treatment of IWR-1， which was an inhibitor of the Wnt/β-catenin signaling pathway， and SAL on cell differentiation. Compared with SAL treatment alone， the combination with SAL and IWR-1 promoted NB4 cell differentiation induced by SAL. These results suggest that SAL effectively inhibits cell proliferation and promotes cell differentiation possibly by blocking of Wnt/β-catenin signaling.
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