Cufí, SílviaBonavia, RosaVazquez Martin, AlejandroOliveras Ferraros, CristinaCorominas Faja, BrunaCuyàs, ElisabetMartin Castillo, BegoñaBarrajón Catalán, EnriqueVisa, JoanaSegura-Carretero, AntonioJoven, JorgeBosch Barrera, JoaquimMicol, VicenteMenendez, Javier A.2018-11-272018-11-272013-08-21https://hdl.handle.net/2445/126451The 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.10 p.application/pdfengcc by (c) Cufí et al., 2013http://creativecommons.org/licenses/by/3.0/es/OncogènesiCàncer de pulmóCarcinogenesisLung cancerinfo:eu-repo/semantics/article2018-07-24info:eu-repo/semantics/openAccess23963283