The mechanism of radiation-induced senescence and the effect for angiogenesis in endothelial cells

电离辐射(IR)对肿瘤血管生成的影响在很大程度上仍不清楚。在本研究中，我们发现在经历指数生长的血管内皮细胞(ECs)中，IR(8Gy射线)诱导了高频率(80-90%)的衰老表型。这一发现使我们能够通过检测这些内皮细胞的基因表达谱和体外血管生成活性来表征IR诱导的类衰老(IRSL)表型。与细胞周期进程和DNA复制相关的基因表达显著减少，体外侵袭和迁移活性通过Matrigel受到明显抑制。我们还发现，融合的内皮细胞在照射后立即复制时表现出高频的IRSL表型，但在平台期条件下孵育减少了表型的诱导，并通过克隆形成确定了细胞存活率。DNA双链断裂(DSB)修复动力学显示融合型ECS的修复时间快于生长期ECS，这可能与前者的IRSL表型保护机制有关。这些结果提示，IRSL表型可能是决定照射后ECS血管生成活性的重要因素。本研究有助于进一步了解IR对肿瘤血管生成的影响。

The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. Expression of genes associated with cell cycle progression and DNA replication was remarkably decreased and in vitro invasion and migration activities through Matrigel of these IRSL ECs were significantly suppressed. We also found that confluent ECs exhibited a high frequency IRSL phenotype when replated immediately after irradiation, but incubation in plateau-phase conditions reduced induction of the phenotype and enhanced cell survival as determined by colony formation. DNA double strand breaks (DSB) repair kinetics showed a faster time course in confluent Ecs than in growing Ecs, which may contribute to the protective mechanism of the IRSL phenotype in the former. These results imply that the IRSL phenotype could be an important factor for determining the angiogenic activity of Ecs following irradiation. The present study should shed additional light on understanding the effect of IR on tumor angiogenesis.