CAJ | 학술논문

目的探讨西妥昔单抗(C225)联合放疗对CNE-2裸鼠移植瘤Ku80和ATM的影响.方法建立CNE-2裸鼠移植瘤模型,将48只裸鼠按随机数字表法分为对照组、常规放疗组(CRT)、模拟调强组(sIMRT)、C225组、CRT+ C225组、sIMRT+ C225组,每组8只.各放疗组给予照射剂量20 Gy,含C225组按1 mg/只给予腹腔内给药.采用RT-PCR方法检测各组肿瘤组织中Ku80和ATM的转录水平,Western blot检测Ku80和ATM蛋白的表达.结果与对照组相比,CRT组、sIMRT组、CRT+ C225组、sIMRT+ C225组的Ku80和ATM的转录水平和蛋白表达均显著下调(P＜0.05).与CRT组相比,sIMRT组ATM下调减弱(P＜0.05),但是放疗联合C225后,CRT+ C225组与CRT组比较和sIMRT+ C225组与sIMRT组比较,ATM下调进一步增强(P＜0.05),sIMRT+ C225组与CRT组的ATM转录水平和蛋白表达的差异无统计学意义(P＞0.05).结论单用C225可使ATM的转录水平和蛋白表达下调,大剂量的照射可使Ku80、ATM的转录水平和蛋白表达均下调；模拟IMRT放疗单次照射时间延长可能引起ATM下调减弱,联合C225后ATM下调增强.
목적 탐토서타석단항(C225)연합방료대CNE-2라서이식류Ku80화ATM적영향.방법 건립CNE-2라서이식류모형,장48지라서안수궤수자표법분위대조조、상규방료조(CRT)、모의조강조(sIMRT)、C225조、CRT+ C225조、sIMRT+ C225조,매조8지.각방료조급여조사제량20 Gy,함C225조안1 mg/지급여복강내급약.채용RT-PCR방법검측각조종류조직중Ku80화ATM적전록수평,Western blot검측Ku80화ATM단백적표체.결과 여대조조상비,CRT조、sIMRT조、CRT+ C225조、sIMRT+ C225조적Ku80화ATM적전록수평화단백표체균현저하조(P＜0.05).여CRT조상비,sIMRT조ATM하조감약(P＜0.05),단시방료연합C225후,CRT+ C225조여CRT조비교화sIMRT+ C225조여sIMRT조비교,ATM하조진일보증강(P＜0.05),sIMRT+ C225조여CRT조적ATM전록수평화단백표체적차이무통계학의의(P＞0.05).결론 단용C225가사ATM적전록수평화단백표체하조,대제량적조사가사Ku80、ATM적전록수평화단백표체균하조；모의IMRT방료단차조사시간연장가능인기ATM하조감약,연합C225후ATM하조증강.
Objective To investigate the effect of cetuximab (C225) combined with radiation on the expressions of Ku80 and ATM in CNE-2 nude mice xenograft tumor model.Methods The CNE2 nude mice xenograft tumor model was established and divided into control group,conventional radiotherapy (CRT) group,simulated intensity modulated radiation therapy (sIMRT) group,C225 group,CRT + C225 group and sIMRT + C225 group with 8 mice in each group.The dose of radiation was 20 Gy,and 1mg C225 per mice in abdominal cavity was applied for the drug treatment.The transcriptional levels of Ku80 and ATM were assayed by RT-PCR and Western blot.Results Compared with control group,the transcriptional and translational levels of Ku80 and ATM in CRT group,sIMRT group,CRT + C225 group and slMRT + C225 group were decreased (P ＜ 0.05).Compared with CRT group,the down-regulation of transcriptional and translational ATM level in sIMRT group was obvious (P ＜ 0.05),and further strengthened in the CRT + C225 group and sIMRT + C225 groups (P ＜0.05),but there was no significant difference of ATM expression between sIMRT + C225 group and CRT group (P ＞ 0.05).Conclusions C225 alone can restrain the transcriptional and translational level of ATM,and the transcriptional and translational level of Ku80 and ATM are also restrained after megadose.ATM is down-regulated by sIMRT but up-regulated by the combination of C225 and radiation.