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光激活底物在评估上皮-间质转化抑制剂中的应用

An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors.

作者信息

Nakanishi Jun, Sugiyama Kenji, Matsuo Hirotaka, Takahashi Yoko, Omura Satoshi, Nakashima Takuji

机构信息

International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS).

Kitasato Institute for Life Sciences, Kitasato University.

出版信息

Anal Sci. 2019 Jan 10;35(1):65-69. doi: 10.2116/analsci.18SDP07. Epub 2018 Nov 2.

Abstract

Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to cell-adhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

摘要

上皮-间质转化(EMT),即细胞黏附和迁移方面的表型变化,参与癌症侵袭和转移,因此成为抗癌药物的作用靶点。在本研究中,我们报告了一种利用光活化金底物评估EMT抑制剂的方法,该底物在光照下会从非细胞黏附性转变为细胞黏附性。该方法基于细胞簇的几何限制以及通过对底物进行可控光照射随后诱导迁移。作为概念验证实验,根据簇面积或领头细胞出现情况的变化,成功评估了一种已知的EMT抑制剂对生化和机械诱导的EMT的反应。此外,将本方法应用于微生物次生代谢产物,鉴定出那波霉素H为一种EMT抑制剂,它可能在扩散条件下杀死发生EMT的细胞。这些结果证明了本方法在筛选新型EMT抑制剂方面的潜力。

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