Ursolic acid reverses hypoxia-driving radioresistance of glioma cells via SENP1/HIF‐1α axis

Glioma is an aggressive brain tumor that is resistant to radiotherapy due to hypoxia, a characteristic of the tumor microenvironment. The role of UA in overcoming radiotherapy resistance in glioma is poorly understood. This study aimed to investigate the effect and mechanism of UA in regulating the SENP1/HIF-1α axis, which reverses the hypoxia-induced radioresistance of glioma cells. U251 glioma cells were cultured under normoxia and hypoxia conditions and exposed to varying doses of radiation. Hypoxia increases the resistance of U251 cells to radiotherapy. UA treatment reversed this tolerance, as evidenced by reducing cell viability and colony formation while increasing apoptosis. UA inhibited the de-SUMOylation activity of SENP1, leading to an increase in SUMO-modified proteins and inhibition of HIF-1α expression. UA can reverse hypoxia-induced radioresistance in glioma cells by modulating the SENP1/HIF-1α axis. UA reverses radioresistance in hypoxia gliomas by targeting SENP1/ HIF-1α, and these findings may provide important insights into developing new strategies to combat glioma radioresistance.