胰岛素样生长因子－1受体抑制剂 AG1024对鼻咽癌移植瘤的放射增敏效应

摘要

目的：探讨胰岛素样生长因子－1受体（ IGF－1R）抑制剂AG1024对裸鼠鼻咽癌移植瘤的放射增敏效应。方法建立人鼻咽癌裸鼠移植瘤模型20只，随机分为A、B、C、D 4组，每组5只。 A组每只瘤注射生理盐水0.3 mL／（次·周），隔天1次，共9次；B组每只瘤注射AG102430 mg／（kg·周），0.3 mL／次，隔天1次，共9次；C组直线加速器6 meV电子线照射，每次局部2 Gy／只，隔天1次，共18 Gy；D组每只瘤注射AG102430 mg／（ kg·周），0.3 mL／次，隔天1次，直线加速器6 meV电子线照射，每次局部2 Gy／只，隔天1次，共18 Gy。观察移植瘤的生长速度和瘤体大小变化；采用流式细胞仪检测细胞凋亡率；采用荧光定量PCR检测PCNA、Survivin mRNA的表达水平。结果 D组鼻咽癌移植瘤的生长显著受抑制，流式细胞仪显示细胞凋亡率明显提高，均明显高于其他3组（ P＜0.05）；D组中的PCNA、Survivin mRNA表达水平均显著低于另外3组（ P＜0.05）。结论 AG1024联合放疗的疗效较单一治疗方案有显著的提高。%Objective To study the radiosensitizing effects of AG1024, the insulin like growth factor-1 receptor (IGF-1R) inhibitor, on the transplanted tumor of nasopharyngeal carcinoma (NPC) in nude mice.Methods The transplanted tumor models of human CNE2 NPC in nude mice were established and randomly divided into four groups, the control, the AG1024, the radiation and the combination therapy groups.The latter three groups were treated with AG1024, radiotherapy, AG1024 combined with radiotherapy, respectively.The growth of transplanted tumor was recor-ded.The apoptosis were examined by flow cytometry.The mRNA expression of PCNA and survivin in tumor samples was assessed by RT-PCR.Results Significant inhibitive effect was observed in combination therapy group, with significantly higher apoptosis rate when comparing with the other 3 groups (P<0.05).Expression levels of PCNA and survivin in the combination therapy group were significantly lower than those in the other 3 groups(P<0.05).Conclusion The combi-nation therapy has obviously higher curative efficacy than simple therapy, providing theoretic and clinical basis for the re-search of combination of targeting treating and radiotherapy.