The Expression of Hypoxia Inducible Factor-1alpha by Desferrioxamine Induces Radioresistance in Mouse Hepatoma Cell Line

Kwon, Byung Hyun

Abstract

PURPOSE: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a pivotal role in the essential adaptive responses to hypoxia. Therefore this study investigated the relationship between HIF-1alpha expression and radiosensitivity.
MATERIALS AND METHODS
Mouse hepatoma cell line hepa1c1c7 and HIF-1beta-deficient mutant cell line hepa1C4 were used to analyze the role of HIF-1alpha on radiosensitivity. These cells were exposed for 6 h to desferrioxamine (DFX) before radiation. HIF-1alpha expression was examined by Western blot. Apoptosis was assessed by DNA fragmentation, propidium iodide staining, and apoptotic cell death detection ELISA kit. Radiation sensitivity was determined using MTT assay. The radiobiological parameters, surviving fractions at 2 Gy and 8 Gy, and mean inactivation dose (MID) from the linear-quadratic model were used to assess radiation sensitivity in the statistical analyses.
RESULTS
The expression of HIF-1alpha was increased, whereas apoptosis was decreased, by radiation in the presence of DFX in hepa1c1c7, but not in hepa1C4. The radiosensitivity of hepa1C4 cells was not significantly affected by DFX treatment. The radiosensitivity of hepa1c1c7 cells was significantly decreased in the presence of DFX
CONCLUSION
The expression of HIF-1alpha by hypoxia-mimic agent DFX reduced apoptosis and radiosensitivity in mouse hepatoma cell line hepa1c1c7. These results suggested that HIF-1alpha could be induced by irradiation in hypoxic cells of tumor masses, and that this might increase radioresistance in hypoxic cells.