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Updated: Apr 22, 2026
Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
DNA-PKcs deficiency inhibits glioblastoma cell-derived angiogenesis after ionizing radiation
Yang Liu1, Luwei Zhang, Yuanyuan Liu
1Department of Radiation Medicine, Institute of Modern physics, Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, China.
Abstract:
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a critical role in non-homologous end-joining repair of DNA double-strand breaks (DSB) induced by ionizing radiation (IR). Little is known, however, regarding the relationship between DNA-PKcs and IR-induced angiogenesis; thus, in this study we aimed to further elucidate this relationship. Our findings revealed that lack of DNA-PKcs expression or activity sensitized glioma cells to radiation due to the defective DNA DSB repairs and inhibition of phosphorylated Akt(Ser473) . Moreover, DNA-PKcs deficiency apparently mitigated IR-induced migration, invasion and tube formation of human microvascular endothelial cell (HMEC-1) in conditioned media derived from irradiated DNA-PKcs mutant M059J glioma cells or M059K glioma cells that have inhibited DNA-PKcs kinase activity due to the specific inhibitor NU7026 or siRNA knockdown. Moreover, IR-elevated vascular endothelial growth factor (VEGF) secretion was abrogated by DNA-PKcs suppression. Supplemental VEGF antibody to irradiated-conditioned media was negated enhanced cell motility with a concomitant decrease in phosphorylation of the FAK(Try925) and Src(Try416) . Furthermore, DNA-PKcs suppression was markedly abrogated in IR-induced transcription factor hypoxia inducible factor-1α (HIF-1α) accumulation, which is related to activation of VEGF transcription. These findings, taken together, demonstrate that depletion of DNA-PKcs in glioblastoma cells at least partly suppressed IR-inflicted migration, invasion, and tube formation of HMEC-1 cells, which may be associated with the reduced HIF-1α level and VEGF secretion. Inhibition of DNA-PKcs may be a promising therapeutic approach to enhance radio-therapeutic efficacy for glioblastoma by hindering its angiogenesis.
Insights
Inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in glioma cells reduces radiation-induced DNA damage and hinders blood vessel formation. This suggests DNA-PKcs inhibition could improve glioblastoma radiotherapy by blocking angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is crucial for repairing DNA double-strand breaks (DSB) after ionizing radiation (IR).
- The role of DNA-PKcs in IR-induced angiogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the relationship between DNA-PKcs and IR-induced angiogenesis in glioma.
- To explore the potential of targeting DNA-PKcs to enhance glioblastoma radio-therapy.
Main Methods:
- Utilized DNA-PKcs mutant M059J and M059K glioma cells with inhibited DNA-PKcs activity (NU7026 inhibitor or siRNA).
- Assessed IR-induced DNA repair, Akt phosphorylation, and human microvascular endothelial cell (HMEC-1) migration, invasion, and tube formation in conditioned media.
- Measured vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) levels.
Main Results:
- DNA-PKcs deficiency sensitized glioma cells to radiation via defective DNA repair and reduced Akt phosphorylation.
- DNA-PKcs suppression mitigated IR-induced HMEC-1 angiogenesis (migration, invasion, tube formation).
- IR-induced VEGF secretion and HIF-1α accumulation were abrogated by DNA-PKcs suppression.
Conclusions:
- DNA-PKcs depletion in glioblastoma cells suppresses IR-induced angiogenesis, potentially through reduced HIF-1α and VEGF.
- Inhibiting DNA-PKcs may represent a therapeutic strategy to enhance radio-therapy efficacy for glioblastoma by targeting angiogenesis.
