Résumé
The aim of this study was to characterize a cell-based model for the molecular study of hypoxia-inducible factor (HIF)-1 alpha activity, in the context of hypoxia, by means of different imaging techniques.
Engineered U251-HRE glioma cells were used to analyze the molecular mechanisms underlying HIF-1 alpha activity in vitro in relation to luciferase expression. The same cells were orthotopically implanted in mice to evaluate tumor progression and hypoxia induction by bioluminescence imaging, fluorescence imaging, positron emission tomography (PET), and magnetic resonance imaging (MRI).
In vitro analyses highlighted the relationship between HIF-1 alpha and luciferase activity in hypoxic conditions and after pharmacological treatments in U251-HRE cells. Through in vivo studies, it was possible to assess hypoxia establishment in relation to tumor growth by optical imaging, PET and MRI.
The findings of this study indicate that the U251-HRE orthotopic murine model can be used to reliably evaluate processes modulating HIF-1 alpha activity, using both molecular and preclinical non-invasive imaging techniques.