FDX1 Regulates the Phosphorylation of ATM, DNA-PKcs Akt, and EGFR and Affects Radioresistance Under Severe Hypoxia in the Glioblastoma Cell Line T98G

Hypoxic cells exhibit radioresistance, which is associated with poor prognosis in cancer patients. Understanding the molecular mechanisms underlying radioresistance in hypoxic tumor cells is crucial for improving radiotherapy efficacy. In this study, we examined the role of FDX1 in regulating cellular responses to severe hypoxia in glioblastoma cell lines T98G and A172. We found that FDX1 expression was upregulated under severe hypoxia, and its knockdown reduced the hypoxia-induced activation of key radioresistance factors and cellular survival mechanisms, including ATM, DNA-PKcs, Akt, and EGFR. FDX1 knockdown also sensitized T98G cells to radiation under severe hypoxia. Furthermore, FDX1 was found to regulate HIF-1α protein level, while HIF-1α did not regulate FDX1 expression. These results suggest that FDX1 may be a novel therapeutic target to overcome radioresistance in glioblastoma under severe hypoxia.