Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer
Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer
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DOI：
10.1016/j.bbrc.2020.06.077
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发表时间：
2020-08-27
影响因子：
3.1
通讯作者：
Toyooka, Shinichi
中科院分区：
文献类型：
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作者：
Ochi, Kosuke;Suzawa, Ken;Toyooka, Shinichi
背景资料：上皮-间质转化（EMT）是肿瘤进展和转移的关键过程，也与耐药性有关。因此，控制EMT状态是一个感兴趣的研究，以征服的恶性tumors.Materials和方法：药物重新定位分析从公共细胞系数据库中的转录组数据确定莫能菌素，一个广泛使用的兽医，作为一个候选EMT抑制剂，抑制EMT表型的转换。结果：TGF-β可诱导非小细胞肺癌（non-small cell lung cancer，NSCLC）细胞发生EMT，EGFR突变型NSCLC细胞对EGFR酪氨酸激酶抑制剂产生耐药。莫能菌素的加入有效地抑制了TGF-β诱导的EMT转化，并恢复了EGFR-酪氨酸激酶抑制剂的生长抑制和诱导凋亡。结论：我们的数据表明，与莫能菌素的联合治疗可能是一个有用的策略，防止EMT介导的获得性耐药。(C)2020爱思唯尔公司All rights reserved.
Background: The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors.Materials and methods: A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-beta-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed.Results: TGF-beta treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-beta-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-beta-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor.Conclusion: Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance. (C) 2020 Elsevier Inc. All rights reserved.