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  • 标题:Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo
  • 本地全文:下载
  • 作者:Sílvia Cufí ; Rosa Bonavia ; Alejandro Vazquez-Martin
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2013
  • 卷号:3
  • 期号:1
  • DOI:10.1038/srep02459
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:The flavolignan silibinin was studied for its ability to restore drug sensitivity to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)-driven resistance to erlotinib. As a single agent, silibinin significantly decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by approximately 50%. Furthermore, the complete abrogation of tumor growth was observed with the co-treatment of erlotinib and silibinin. Silibinin fully reversed the EMT-related high miR-21 /low miR-200c microRNA signature and repressed the mesenchymal markers SNAIL , ZEB , and N-cadherin observed in erlotinib-refractory tumors. Silibinin was sufficient to fully activate a reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC cells. Given that the various mechanisms of resistance to erlotinib result from EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk thistle extract might be a suitable candidate therapy for upcoming clinical trials aimed at preventing or reversing NSCLC progression following erlotinib treatment.
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