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Sci Rep ; 11(1): 8091, 2021 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-33854147

RESUMEN

Drug repositioning refers to new uses for existing drugs outside the scope of the original medical indications. This approach fastens the process of drug development allowing finding effective drugs with reduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment affects viability, epithelial-mesenchymal transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment affects different steps leading to metastasis in TNBC. Moreover, combined treatment is also effective preventing the development of 5-FU resistant CRC. Our data suggest that combination of metformin and propranolol could be useful as a putative adjuvant treatment for both TNBC and CRC and an alternative for chemo-resistant CRC, providing a low-cost alternative therapy without associated toxicity.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Reposicionamiento de Medicamentos , Metformina/uso terapéutico , Propranolol/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Quimioterapia Combinada , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Humanos , Metformina/farmacología , Ratones , Ratones Desnudos , Propranolol/farmacología , Trasplante Heterólogo , Neoplasias de la Mama Triple Negativas/patología , beta Catenina/metabolismo
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