The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells
The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells
复制标题
DOI：
10.1016/j.ygyno.2013.03.005
复制
发表时间：
2013-06-01
影响因子：
4.7
通讯作者：
Takeda, Satoru
中科院分区：
文献类型：
--
作者：
Kusunoki, Soshi;Kato, Kiyoko;Takeda, Satoru
的目标。我们之前已经证明，人子宫内膜癌细胞（Hec1细胞）和表达致癌的人K-Ras蛋白（RK12V细胞）的大鼠子宫内膜细胞中的侧群（SP）细胞具有癌症干细胞（CSCs）的特征。he1 - sp细胞表现出增强的迁移能力和向间充质细胞谱系分化的潜力。在这项研究中，我们分析了上皮-间质转化（EMT）与这些子宫内膜间质干细胞特性的关系。我们还利用he1 -sp细胞评估了盐霉素（一种具有emt特异性毒性的化合物）对这些子宫内膜CSCs的增殖能力、迁移能力和侵袭性的影响。我们使用一组RK12V-SP细胞和-非sp （NSP）细胞进行微阵列表达分析，筛选CSCs中上调基因，并使用Metacore软件包鉴定与上调基因相关的Gene GO通路map。为了分析其与EMT的关系，我们采用real - time PCR检测了几种EMT相关基因在Hec1-SP细胞中的表达，并与Hec1-NSP细胞中的表达进行了比较。实时荧光定量PCR检测BAX、BCL2、LEF1、cyclinD和纤维连接蛋白的表达。我们还评估了这些SP细胞和NSP细胞在存在或不存在盐霉素的情况下的生存能力、迁移和侵袭活性以及致瘤性。结果表明：1)在RK12V-SP细胞和Hec1-SP细胞中均观察到EMT过程；2)在Hec1-SP细胞中纤维连接蛋白水平升高，而盐霉素降低了纤维连接蛋白的表达水平；3)盐霉素诱导细胞凋亡并抑制Wnt信号传导；4)盐霉素抑制了这些SP细胞的增殖、迁移、侵袭和致瘤性。本文首次报道了盐霉素对子宫内膜CSCs的抑制作用。(c) 2013爱思唯尔公司版权所有。
Goals. We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs. We also assessed the effects of salinomycin (a compound with EMT-specific toxicity) on the proliferative capacity, migration and invasiveness of these endometrial CSCs using Hec1-SP cells.Method. We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP(NSP) cells and Used the Metacore package to identify the Gene GO pathway MAPs involved in the up-regulated genes. To analyze their association with EMT, the expression of several EMT associated genes in Hec1-SP cells was investigated by real time PCR and compared with that in Hec1-NSP cells. We assessed the expression of BAX, BCL2, LEF1, cyclinD and fibronectin by real time PCR. We also evaluated the viabilities, migration and invasive activities, and tumorigenicities of these SP cells and NSP cells in the presence or absence of salinomycin.Results. We demonstrated that i) EMT processes were observed in both RK12V-SP cells and Hec1-SP cells, ii) the level of fibronectin was enhanced in Hec1-SP cells and salinomycin reduced the level of fibronectin expression, iii) salinomycin induced apoptosis and inhibited Wnt signaling, and iv) salinomycin inhibited the proliferation, migration, invasiveness and tumorigenicity of these SP cells.Conclusion. This is the first report of an inhibitory effect of salinomycin on the properties of endometrial CSCs. (c) 2013 Elsevier Inc. All rights reserved.