Activación de STAT3 por hipoxia en modelos in vitro de cáncer de cuello uterino y en células endoteliales

  • Óscar Ortega Grupo de Investigación en Bioquímica y Biotecnología, Universidad del Rosario, Bogotá, D.C., Colombia
  • Alejandro Ondo-Méndez Grupo de Investigación en Bioquímica y Biotecnología, Universidad del Rosario, Bogotá, D.C., Colombia
  • Ruth Garzón Grupo de Investigación en Bioquímica y Biotecnología, Universidad del Rosario, Bogotá, D.C., Colombia
Palabras clave: factores de transcripción STAT, hipoxia de la célula, neoplasias del cuello uterino, células endoteliales, microambiente tumoral, células HeLa, estrés fisiológico

Resumen

Introducción. El microambiente tumoral influye en el comportamiento de las células cancerosas. Especialmente, el estímulo de agentes estresantes, como la hipoxia, se convierte en un factor crítico para la evolución y el tratamiento del cáncer. La reacción celular frente a diversos estímulos se manifiesta en la activación de vías de señalización como la JAK/STAT, una de las más importantes por sus efectos en la diferenciación y proliferación celular.
Objetivo. Evaluar el estado de la vía JAK/STAT mediante la expresión o activación de la proteína STAT3 en células de cáncer de cuello uterino (HeLa) y en células endoteliales (EA.hy926) sometidas a hipoxia.
Materiales y métodos. Las líneas celulares se sometieron a condiciones de hipoxia física (1 % de O2) o química (100 μM de deferoxamina, DFO) durante dos, seis y 24 horas. Mediante Western blot se determinó el cambio en la expresión y activación de STAT3, y mediante inmunofluorescencia indirecta, su localización subcelular.
Resultados. La hipoxia se evidenció por la activación y translocación al núcleo del HIF-1. Ni la hipoxia física ni la química alteraron la expresión de STAT3, pero sí la activación, según se comprobó por su fosforilación y su translocación al núcleo en los dos modelos bajo estudio.
Conclusiones. Se evidenció la importancia de la hipoxia como un estímulo que modifica la activación de la proteína STAT3 en las células HeLa y EA.hy926, lo cual la convierte en un elemento importante en el diseño de estrategias terapéuticas contra el cáncer.

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Publicado
2017-01-24
Cómo citar
Ortega, Óscar, Ondo-Méndez, A., & Garzón, R. (2017). Activación de STAT3 por hipoxia en modelos in vitro de cáncer de cuello uterino y en células endoteliales. Biomédica, 37(1), 119-130. https://doi.org/10.7705/biomedica.v37i2.3225
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Artículos originales