Affiliation:
1. Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin China
2. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Tianjin China
3. Tianjin Institutes of Health Science Tianjin China
4. State Key Laboratory of Advanced Medical Materials and Devices Tianjin China
Abstract
Abstractl‐2‐Hydroxyglutarate (l‐2‐HG) has been regarded as a tumor metabolite, and it plays a crucial role in adaptation of tumor cells to hypoxic conditions. However, the role of l‐2‐HG in tumor radioresistance and the underlying mechanism have not yet been revealed. Here, we found that l‐2‐HG exhibited to have radioresistance effect on U87 human glioblastoma cells, which could reduce DNA damage and apoptosis caused by irradiation, promote cell proliferation and migration, and impair G2/M phase arrest. Mechanistically, l‐2‐HG upregulated the protein level of hypoxia‐inducible factor‐1α (HIF‐1α) and the expression levels of HIF‐1α downstream target genes. The knockdown of l‐2‐hydroxyglutarate dehydrogenase (L2HGDH) gene promoted the tumor growth and proliferation of U87 cells in nude mice by increasing HIF‐1α expression level in vivo. In addition, the low expression level of L2HGDH gene was correlated with the short survival of patients with glioma or kidney cancer. In conclusion, our study revealed the role and mechanism of l‐2‐HG in tumor radioresistance and may provide a new perspective for overcoming tumor radioresistance and broaden our comprehension of the role of metabolites in tumor microenvironment.