摘要
目的:研究COX-2抑制剂NS-398对结肠癌细胞系HT-29的放射增敏作用及其相关放射增敏机制。方法:25μmol/L NS-398预处理HT-29细胞24 h后给不同剂量X线照射,以克隆形成实验检测NS-398放射增敏作用。DNA凝胶电泳、流式细胞仪检测细胞凋亡。分光光度法测定Caspase38、、9活性。结果:25μmol/L NS-398对HT-29细胞有放射增敏作用,由Dq、D0计算放射增敏比(SER)分别为1.361、.27。NS-398可以增强HT-29细胞的放射诱导凋亡敏感性,DNA凝胶实验中观察到典型的DNA“Ladder”。与照射组比较,NS-398预处理组细胞凋亡指数及Caspase3、89、活性均增高(P<0.05),且Caspase39、活性增高更为明显。结论:COX-2抑制剂NS-398在HT-29细胞中具有放射增敏作用,诱导细胞凋亡是其放射增敏的重要机制之一。
Objective： To investigate the radiosensitizing effect and mechanisms of COX-2 inhibitor NS-398 on the colorectal cancer cell line HT-29. Methods： The colorectal cancer cell line HT-29 had been incubated with 25 μmol/L NS-398 for 24h before X-ray irradiation at different doses（0, 2, 4, 6 and 8 Gy）. The cells were assayed for clonogenic survival to determine the radiosensitizing effect of NS-398. HT-29 cell apoptosis was confirmed by DNA fragmentation （DNA ladder, sub-G1 formation）. Caspase 3, 8 and 9 activation were measured by spectrophotometry. Results： The sensitization enhanonmnt ratios in HT-29 cells were 1.36 and 1.27 according to Dq and Do respectively. The typical DNA ＂Ladder＂ and higher sub-G1 cell peak were observed in the NS-398 pre-treatment group after irradiation. Caspase3, 8 and 9 activation of the HT-29 cells with pretreatment of 25 tmaol/L NS-398 for 24 h increased after irradiation, especially caspase 3 and 9. Condusion： The COX-2 inhibitor NS-398 has a radiosensitizing effect on HT-29 cells, and this mechanism may be closely associated with the increase of the sensitivity of HT-29 to X-my irradiation-induced apoptosis.
出处
《山东大学学报（医学版）》
CAS
北大核心
2007年第2期152-154,159,共4页
Journal of Shandong University:Health Sciences
基金
山东省自然科学基金资助课题(Z2005Co2)
