王若峥,胡云辉,黄莉,于金明.西妥昔单抗联合放疗对CNE-2裸鼠移植瘤Ku80和ATM表达的影响[J].中华放射医学与防护杂志,2013,33(4):351-354
西妥昔单抗联合放疗对CNE-2裸鼠移植瘤Ku80和ATM表达的影响
Effect of cetuximab combined with radiation on the expressions of Ku80 and ATM in CNE-2 nude mice xenograft tumor model
投稿时间:2012-12-13  
DOI:10.3760/cma.j.issn.0254-5098.2013.04.004
中文关键词:  西妥昔单抗  CNE-2  Ku80  ATM
英文关键词:Cetuximab  CNE-2  Ku80  ATM
基金项目:新疆维吾尔自治区国际合作项目(201141138)
作者单位E-mail
王若峥 830011乌鲁木齐, 新疆医科大学附属肿瘤医院头颈放疗科  
胡云辉 830011乌鲁木齐, 新疆医科大学附属肿瘤医院头颈放疗科  
黄莉 830011乌鲁木齐, 新疆医科大学附属肿瘤医院头颈放疗科  
于金明 山东省肿瘤医院放疗科 yujinmingsd@yahoo.com.cn 
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中文摘要:
      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。
英文摘要:
      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 sIMRT+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.
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