摘要目的 研究125I粒子持续低剂量率照射对人食管癌细胞系KYSE150的抑制作用及其机制.方法 根据不同照射方式,将KYSE150细胞分成空白对照组、高剂量率单次外照射组(SDR,1.052 Gy/min)、持续低剂量率照射组(125 I-CLDR,2.77 cGy/h).克隆形成实验衡量KYSEI50细胞对两种照射方式的敏感性,计算125I-CLDR的相对生物学效应(RBE).流式细胞仪分析不同照射方式对细胞凋亡和周期的影响.蛋白免疫印迹法检测不同照射方式下KYSE150细胞内γ-H2AX和Bax的蛋白表达量变化.结果 KYSE150细胞对125I-CLDR的放射敏感性高于SDR,125I-CLDR的相对生物学效应约为1.56;与SDR相比,125I-CLDR能更显著地诱导KYSE150细胞的早期和晚期凋亡(=4.07,11.08,P＜0.05),提高G2/M期细胞比例(t=11.25,P＜0.05);125I-CLDR组DNA损伤信号蛋白γ-H2AX和促凋亡蛋白Bax的表达水平显著升高.结论 与SDR相比,125I-CLDR对人食管癌细胞KYSE150的抑制作用更为显著,其主要机制可能是电离辐射后肿瘤细胞克隆形成能力受损,DNA损伤严重,细胞凋亡增多,而G2/M期细胞比例升高,细胞放射敏感性增强.

abstractsObjective To determine the biological effectiveness of 125I radioactive seeds with continuous low dose rate radiation on the human esophageal cancer cell line KYSE150 in vitro and explore the underlying cellular mechanisms.Methods The cells were divided into three cell groups:control group,single dose radiation group (SDR) and 125I radioactive seeds with continuous low dose rate radiation group (125 I-CLDR).The KYSE150 cells were exposed to radiation of X-ray at a high dose rate of 1.052 Gy/min or 125I radioactive seeds at a low dose rate of 2.77 cGy/h.The responses of KYSE150 cells to two modes of irradiation were evaluated by the colony-forming assay,cell apoptosis as well as cell cycle analysis.Furthermore,the expression levels of γ-H2AX and Bax were detected by Western blot.Results KYSE150 cells were more radiosensitive to 125I-CLDR than SDR.The relative biological effectiveness (RBE) for 125I-CLDR related to SDR was 1.56.Compared with SDR,125I-CLDR yielded more proportions of the early and late apoptosis rate (t =4.07,11.08,P ＜0.05) as well as cells at G2/M phase (t =11.25,P ＜0.05).Moreover,γ-H2AX and Bax expression levels in 125I-CLDR significantly increased compared with SDR.Conclusions Compared with the high dose rate X-ray radiation,the continuous low dose rate radiation of 125I radioactive seeds had stronger inhibition effect on KYSE150 esophageal cancer cells by impairing clonogenic capacity,inducing apoptosis and G2/M cell cycle arrest,and increasing radiosensitivity.