Salinomycin inhibits osteosarcoma by targeting its tumor stem cells
Salinomycin inhibits osteosarcoma by targeting its tumor stem cells
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盐霉素通过靶向肿瘤干细胞抑制骨肉瘤
DOI：
10.1016/j.canlet.2011.07.016
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发表时间：
2011-12-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Tang, Qing-Lian;Zhao, Zhi-Qiang;Wang, Jin
骨肉瘤是儿童和青少年中最常见的原发性骨肿瘤，通常与不良预后相关。肿瘤干细胞（TSC）被认为驱动肿瘤发生和肿瘤复发或转移。因此，骨肉瘤的不良预后可能是由于未能靶向骨肉瘤干细胞造成的。在这里，我们利用三种不同的方法来富集骨肉瘤中的 TSC，并进一步评估盐霉素是否可以选择性地靶向骨肉瘤中的 TSC。我们的结果表明，肌球选择、化疗选择和干细胞标志物 OCT4 或 SOX2 过表达均能有效富集骨肉瘤细胞系中的 TSC。进一步研究发现，盐霉素在体外和体内均通过选择性靶向其干细胞来抑制骨肉瘤，且没有严重的副作用，并且Wnt/β-catenin信号通路可能参与了盐霉素的这种抑制作用。综上所述，我们发现盐霉素是骨肉瘤干细胞的有效抑制剂，支持使用盐霉素消除骨肉瘤干细胞，并意味着需要进一步的临床评估。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Osteosarcoma is the most common primary bone tumor in children and adolescents and is typically associated with a poor prognosis. Tumor stem cells (TSCs) are presumed to drive tumor initiation and tumor relapse or metastasis. Hence, the poor prognosis of osteosarcoma likely results from a failure to target the osteosarcoma stem cells. Here, we have utilized three different methods to enrich TSCs in osteosarcoma and further evaluated whether salinomycin could selectively target TSCs in osteosarcoma. Our results indicated that sarcosphere selection, chemotherapy selection and stem cell marker OCT4 or SOX2 over-expression are all effective in the enrichment of TSCs from osteosarcoma cell lines. Further investigation found that salinomycin inhibited osteosarcoma by selectively targeting its stem cells both in vitro and in vivo without severe side effects, and the Wnt/beta-catenin signaling pathway may be involved in this inhibition of salinomycin. Taken together, we have identified that salinomycin is an effective inhibitor of osteosarcoma stem cells, supporting the use of salinomycin for elimination of osteosarcoma stem cells and implying a need for further clinical evaluation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.