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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126451
Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo
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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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CUFÍ, Sílvia, BONAVIA, Rosa, VAZQUEZ MARTIN, Alejandro, OLIVERAS FERRAROS, Cristina, COROMINAS FAJA, Bruna, CUYÀS, Elisabet, MARTIN CASTILLO, Begoña, BARRAJÓN CATALÁN, Enrique, VISA, Joana, SEGURA-CARRETERO, Antonio, JOVEN, Jorge, BOSCH BARRERA, Joaquim, MICOL, Vicente, MENENDEZ, Javier a.. Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo. _Scientific Reports_. 2013. Vol. 3. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/126451]