Factor inducible por hipoxia HIF-1α modula la resistencia a drogas en células de cáncer de colon

Martha Leonor Pinzón-Daza, Yenith Cuellar, Alejandro Ondo, Luisa Matheus, Lilia Del Riesgo, Fabio Castillo, Ruth Garzón

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1α, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated. Objective: The purpose of this study was to evaluate the effect of HIF-1α activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells. Materials and methods: HT29 colon cancer cells were treated with Cobalt(II) chloride (CoCl2) or doxorubicin and the activity of HIF-1α was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis. Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner. Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1α and the amount of reactive oxygen species generated.

Título traducido de la contribuciónHypoxia-inducible factor HIF-1α modulates drugs resistance in colon cancer cells
Idioma originalEspañol
Páginas (desde-hasta)543-550
Número de páginas8
PublicaciónRevista Facultad de Medicina
Volumen66
N.º4
DOI
EstadoPublicada - oct 1 2018

All Science Journal Classification (ASJC) codes

  • Medicina (todo)

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