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Revista de la Facultad de Medicina
versão impressa ISSN 0120-0011
Resumo
PINZON-DAZA, Martha Leonor et al. Hypoxia-inducible factor HIF-1α modulates drugs resistance in colon cancer cells. rev.fac.med. [online]. 2018, vol.66, n.4, pp.543-550. ISSN 0120-0011. https://doi.org/10.15446/revfacmed.v66n4.55149.
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.
Palavras-chave : Apoptosis; Cell Hypoxia; Colon Cancer; Doxorubicin (MeSH).