摘要
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a critical role in non-homologous end-joiningrepair of DNA double strand breaks (DSB) induced by ionizing radiation (IR) [1]. Little is known, however, regardingthe relationship between DNA-PKcs and IR induced angiogenesis; thus, in this study we aimed to further elucidatethis relationship. Our findings revealed that lack of DNA-PKcs expression or activity sensitized glioma cells toradiation due to the defective DNA DSB repairs and inhibition of phosphorylated Akt Ser473. Moreover, DNAPKcsdeficiency apparently mitigated IR-induced migration, invasion and tube formation of human microvascularendothelial cell (HMEC-1) in conditioned media derived from irradiated DNA-PKcs mutant M059J glioma cells orM059K glioma cells that have inhibited DNA-PKcs kinase activity due to the specific inhibitor NU7026 or siRNAknockdown(Fig. 1).
基金
Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundationof China (11305224, 11205219,11175222).