盐霉素抑制急性早幼粒细胞白血病细胞增殖并诱导分化

Salinomycin Inhibits Acute Promyelocytic Leukemia Cells Proliferation and Induces Differentiation

该文旨在探讨盐霉素(salinomycin,SAL)对急性早幼粒细胞白血病NB4细胞增殖和分化的影响及其可能的机制。采用CCK-8(cell counting kit-8)实验检测细胞增殖,瑞氏染色观察细胞形态学变化,流式细胞术检测粒细胞分化标志物CD11b的表达,Western blot检测相关蛋白质水平变化。结果显示,SAL抑制了细胞增殖;SAL作用72 h后,细胞呈现典型分化形态学改变。随着SAL的浓度升高,CD11b阳性的细胞比例以及CD11b、C/EBPβ蛋白质水平逐渐增加。此外,SAL降低了β-catenin以及下游分子C-myc、Cyclin D1的蛋白质水平。该研究还探讨了联合使用Wnt/β-catenin信号通路的抑制剂IWR-1与SAL对细胞分化的影响。结果显示,与单独使用SAL相比,联合使用SAL和IWR-1促进了SAL诱导的NB4细胞分化。该研究结果提示,SAL可抑制NB4细胞的增殖,并可能通过抑制Wnt/β-catenin信号通路诱导细胞分化。

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 CD1 lb was detected by flow cytometry. The protein levels of CD1 lb, C/EBPI3, 13-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 percentageof CDllb-positive cells and protein levels of CDllb and C/EBP 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.