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Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening

聚焦生物添加于 2009-8-20 01:40 | 2510 次阅读 | 0 个评论

作者
Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES
摘要
Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.
详细资料
- 文献种类:期刊
- 期刊名称: Cell
- 期刊缩写: Cell
- 期卷页: 2009年
- ISBN: 0092-8674
标签

干细胞肿瘤药物筛选高通量筛选
相关链接 DOI URL

聚焦生物的文献笔记订阅

长期来，人们一直期望能找到一种能特异性地抑制上皮肿瘤干细胞（cancer stem cells，CSCs）的药物，来治疗乳腺癌等病症。但是由于该细胞在肿瘤细胞群中分布之稀少，以及体外培养时的不稳定性，使得寻找这样一种药物的目标远不可及。在本期Cell上，MIT和哈佛的学者发布了一种高通量的筛选方法；籍此筛选得到的化学物--salinomycin，对上皮CSC具有选择性的毒性作用。其对乳腺CSC的抑制作用，是临床常用的化疗药paclitaxel的100倍。对小鼠施以salinomycin，能抑制乳房肿瘤的生长，及诱导肿瘤细胞在上皮组织中的分化。随后进行系统性的基本表达谱分析，发现可降低人源CSC基因的表达。这一研究结果揭示：利用本文介绍的方法，可筛选到对 CSC具有选择性抑制作用的药物。

本文的启示意义在于：这种特异性抑制物的筛选方法，以及作者从哪些角度阐述了其作用是“特异性”的。对于类似从事肿瘤药物研究有借鉴作用。

该读书笔记来自丁香园的freecell网友，写得不错，摘了过来和大家分享。

抗肿瘤干细胞药物筛选