UNASSIGNED: Recently several laboratories have reported that radiation induces senescence in endothelial cells. Senescent cells can secrete multiple growth-regulatory proteins, some of which affect @entity5 growth, survival, invasion or angiogenesis. The purpose of this study was to explore the mechanisms of radiation-induced senescence and its effects on angiogenesis in @entity1 umbilical vein endothelial cells (HUVECs). HUVECs were either pretreated with or without @entity38308 prior to irradiation with 0-8 Gy. @entity38308 is a novel, highly specific small-molecule inhibitor of nuclear factor kappa B essential modulator ( @entity10190 ). MTT assays showed that in HUVECs untreated with @entity38308 , there was an increase in the number of radiation-induced senescence-like endothelial cells 5 days after 8 Gy irradiation, while pretreatment with @entity38308 significantly ameliorated the induction in senescence of HUVECs compared to the control group. Electrophoretic mobility shift assay (EMSA) showed that pretreatment with @entity38308 inhibited the radiation-induced NF-kB activation, which regulates cell fate in response to genotoxic stress. In addition, Western blotting demonstrated less translocation of @entity9135 from cytoplasm to nucleus. Furthermore, real-time polymerase chain reaction (PCR) showed that pretreatment with @entity38308 inhibited the increase of mRNA expressions of @entity650 ( @entity650 ) and @entity876 -induced death domain (PIDD) protein, which have been show to play crucial roles in both senescence and apoptosis (P < 0.05). TUNEL staining revealed an increase in apoptotic HUVECs in the group pretreated with @entity38308 after irradiation. The series of functional assays further showed that radiation-induced senescence-like HUVECs had malfunctions in migration, invasion and formation of capillary-like structures, compared with the sham-irradiated and untreated, irradiated groups. Taken together, these findings indicate that the angiogenic capacity of radiation-induced senescence-like HUVECs decreased, and that irradiation caused vascular endothelial cells to gain a senescence-like phenotype through the DSB/ @entity10190 /NF-kB signal pathway. The data suggests that @entity10190 may be a critical switch that regulates cellular senescence and apoptosis caused by exposure to radiation, and provides new clues for the clinical potential of the combination of radiotherapy and angiogenesis inhibitors.

@entity10190 Modulates Radiation-Induced Endothelial Senescence of XXXX Umbilical Veins Through NF-kB Signal Pathway.

@entity1 :: ('9606', 'Species') :: ['human'] @entity9135 :: ('5970', 'Gene') :: ['p65'] @entity650 :: ('3569', 'Gene') :: ['IL-6', 'interleukin-6'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity38308 :: ('MESH:C456319', 'Chemical') :: ['PS1145'] @entity10190 :: ('8517', 'Gene') :: ['NEMO'] @entity876 :: ('7157', 'Gene') :: ['p53']
@entity1 :: (9606,Species) :: ['Human']
