Irradiation effect on telomerase- and angiogenesis-related gene in human umbilical vein endothelial cells.

Abstract

e21048 Background: Radiotherapy is important in the treatment of many human cancers, but the effect of irradiation on angiogenesis still remains largely unknown. We investigated the effects of irradiation on telomerase- and angiogenesis-related genes in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs at passage number (PN)1, PN2 and PN3, respectively, were exposed to irradiation (2 Gy). Changes in cellular growth, senescence, telomerase activity, and expression of telomerase-, angiogenesis- and pan-endothelial marker-related genes were then investigated. Results: Both senescence and growth delay were observed in irradiated HUVECs. Compared to controls, telomerase activity, expression of human telomerase reverse transcriptase (hTERT) and c-myc in irradiated HUVECs were down-regulated in all PNs, and Mad1 was up-regulated at PN3. Down-regulation of vascular endothelial growth factor (VEGF) was observed in irradiated HUVECs as PN increased. Other angiogenesis-related factors [vascular endothelial growth factor receptor (VEFGR)-1, VEGFR-2, VEGFR-3, Tie-1, and Tie-2] and pan-endothelial cell markers [collagen type IV alpha 2, collagen type VI alpha 1, collagen type XVIII alpha 1, insulin-like growth factor-binding protein (IGFBP)-4, IGFBP-7, connective tissue growth factor, interferon-induced transmembrane protein, melanoma cell adhesion molecule, and von Willebrand factor] were also down-regulated in irradiated HUVECs. Conclusions: Irradiation at doses relevant to clinical radiotherapy can induce endothelial cell senescence. Irradiation-induced cell senescence could be related with the down-regulation of hTERT. Change in the expression of c-Myc, Mad1, and VEGF could contribute to the irradiation-induced down-regulation of hTERT.