SIRT2 Suppression Increases Responsiveness of Glioma Cells to Radiation Treatment via FoxO3a Inhibition

Due to the resistance to radiotherapy, the prognosis of patients with glioblastoma multiforme (GBM) is poor despite standard treatment. Forkhead Box O3 (FoxO3a) is reported to mediate multiple pathological processes involved in proliferation, apoptosis, and DNA repair processes, and associated with poor prognosis of GBM. Further work is required to explore the role of FoxO3a in GBM radioresistance. RT-qPCR indicated that FoxO3a was significantly up-regulated in GBM cells in response to radiation. Knockdown of FoxO3a enhances the responsiveness of GBM cells to radiotherapy. After radiation stimulation, the clonogenic capacity of the cells with FoxO3a knockdown (KD) was much weaker than that of the normal control group (NC), while the degree of DNA damage detected by the comet assay was significantly higher in the cells with FoxO3a knockdown. Moreover, combining recent research, we demonstrated that suppression of SIRT2 down-regulated FoxO3a with radiation therapy by Western Blot. DNA damage assay and comet assay indicated that the degree of DNA damage increased in the cells of SIRT2 knockdown compared to the normal control (NC). The study indicated that suppression of SIRT2 increased the sensitivity of GBM cells to radiotherapy via FoxO3a inhibition and provided a novel idea for overcoming radioresistance in GBM.