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沙利霉素选择性靶向“CD133+”细胞亚群,并降低结直肠癌细胞系的恶性特征。

Salinomycin selectively targets 'CD133+' cell subpopulations and decreases malignant traits in colorectal cancer lines.

机构信息

Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

出版信息

Ann Surg Oncol. 2011 Jun;18(6):1797-804. doi: 10.1245/s10434-011-1561-2. Epub 2011 Jan 26.

Abstract

BACKGROUND

Cancer stem-like cells (CSCs) in colorectal cancers (CRC) may account for the failure of treatments because they are resistant to many current anticancer therapies. Salinomycin, a potassium ionophore, was recently identified as a selective inhibitor of breast CSCs.

METHODS

The human CRC cell lines HT29 and SW480 were treated with salinomycin and oxaliplatin. Cell viability was determined with cell counting kit 8. Fraction of CD133+ cell subpopulations was assessed by Flow Cytometric analysis. Clonogenecity and migration were determined with soft agar and Boyden chamber assays. Molecular changes were assessed by immunofluorescence staining, RT-PCR, and Western blot analysis.

RESULTS

We report that salinomycin reduces the proportion of CD133+ subpopulations in human CRC HT29 and SW480 cells. Furthermore, salinomycin treatment decreases colony-forming ability and cell motility in HT29 cells. Moreover, salinomycin downregulates the expression of vimentin and induces the E-cadherin expression in HT29 cells.

CONCLUSIONS

This study demonstrates the ability of salinomycin to selectively target "CD133+" cell subpopulations and decrease the malignant traits in colorectal cancer lines.

摘要

背景

结直肠癌细胞(CRC)中的癌症干细胞(CSC)可能导致治疗失败,因为它们对许多现有的抗癌疗法具有抗性。沙利霉素是一种钾离子载体,最近被鉴定为乳腺癌 CSC 的选择性抑制剂。

方法

用沙利霉素和奥沙利铂处理人 CRC 细胞系 HT29 和 SW480。用细胞计数试剂盒 8 测定细胞活力。通过流式细胞术分析评估 CD133+细胞亚群的比例。通过软琼脂和 Boyden 室测定测定克隆形成能力和迁移能力。通过免疫荧光染色、RT-PCR 和 Western blot 分析评估分子变化。

结果

我们报告沙利霉素降低了人 CRC HT29 和 SW480 细胞中 CD133+亚群的比例。此外,沙利霉素处理降低了 HT29 细胞的集落形成能力和细胞迁移能力。此外,沙利霉素下调了 HT29 细胞中波形蛋白的表达,并诱导了 E-钙黏蛋白的表达。

结论

这项研究表明沙利霉素能够选择性地靶向“CD133+”细胞亚群,并降低结直肠癌细胞系的恶性特征。

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