NS-398对结肠癌细胞系HT-29放射增敏作用的观察

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24h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Caspase3、8、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1.36、1.27。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、8、9活性均增高（P＜0.05）,且Caspase3、9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。

Radiosensitivity enhancement by NS-398,a cyclooxygenase(COX)-2 selective inhibitor,via enhancing the sensitivity to X-ray irradiation-induced apoptosis on the human colorectal cancer cell line HT-29

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 25μmol/L NS-398 for 24h before X-ray irradiation at different doses(0, 2, 4, 6 and 8Gy). 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 enhancement ratios in HT-29 cells were 1.36 and 1.27 according to Dq and D0 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 25μmol/L NS-398 for 24h increased after irradiation, especially caspase 3 and 9. Conclusion： 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-ray irradiation induced apoptosis.