Rapamycin inhibited the function of lung CSCs via SOX2
Rapamycin inhibited the function of lung CSCs via SOX2
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DOI：
10.1007/s13277-015-4341-y
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
L. Xie;Fengfei Sun;B. He;Xiao-feng Zhan;Juan Song;Sheng‐Song Chen;Shi-cang Yu;Xiaoqun Ye
中科院分区：
文献类型：
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作者：
L. Xie;Fengfei Sun;B. He;Xiao-feng Zhan;Juan Song;Sheng‐Song Chen;Shi-cang Yu;Xiaoqun Ye
癌症干细胞（CSC）的存在是肺癌发生、恶化和复发的根源。因此，靶向杀死肺部CSC被认为是治疗肺癌的有效方法。在这项研究中，我们发现雷帕霉素抑制A549细胞中的哺乳动物雷帕霉素靶点（mTOR）信号转导，并提高对顺铂（DDP）的敏感性。其机制涉及抑制 SOX2 表达、细胞增殖、上皮间质转化 (EMT) 表型和球体形成。有趣的是，在 A549 球体中，敲低 SOX2 与雷帕霉素具有相似的效果。此外，我们发现 A549 细胞中 Sox2 的异位表达足以使其对体外雷帕霉素治疗更具抵抗力。这些数据表明雷帕霉素通过 SOX2 抑制肺 CSC 的功能。进一步探索肺癌的治疗策略将具有很大的意义。
The presence of cancer stem cells (CSCs) is the source of occurrence, aggravation, and recurrence of lung cancer. Accordingly, targeting killing the lung CSCs has been suggested to be an effective approach for lung cancer treatment. In this study, we showed that rapamycin inhibited the mammalian target of rapamycin (mTOR) signal transduction in A549 cells and improved the sensitivity to cisplatin (DDP). The mechanisms involve inhibition of the SOX2 expression, cell proliferation, epithelial-mesenchymal transition (EMT) phenotype, and sphere formation. Interestingly, knocked down SOX2 was a similar effect with rapamycin in A549 sphere. Furthermore, we showed that ectopic expression of Sox2 in A549 cells was sufficient to render them more resistant to rapamycin treatment in vitro. These data suggested that rapamycin inhibited the function of lung CSCs via SOX2. It will be of great interest to further explore the therapeutic strategies of lung cancer.