胰岛素样生长因子1受体抑制剂对人食管癌移植瘤放射增敏研究  

Radiosensitization of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts

作　　者：吴广银[1] 韩倩[1] 朱庆尧[1] 李良[1] 李鑫[2] 

机构地区：[1]河南省人民医院放疗科,郑州450003 [2]郑州大学第一附属医院肿瘤科

出　　处：《中华放射医学与防护杂志》2013年第4期376-379,共4页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的 观察胰岛素样生长因子1受体（IGF-1R）抑制剂AG1024对裸鼠EC9706食管癌模型的放射增敏作用及机制.方法 裸鼠皮下接种人食管癌EC9706细胞建立模型,待肿瘤长至100 mm3时按随机表将小鼠分成4组,对照组、单纯照射组、AG1024组、联合组.对照组：不处理；单纯照射组：第1、8天分别给予6MVX射线,照射剂量单次8 Gy；AG1024组：AG1024腹腔注射30 μg/（kg·d）,每周5次,共2周；联合组：给予AG1024腹腔注射和照射.每隔2天测肿瘤直径,第15天断颈处死小鼠计算抑瘤率.流式细胞仪检测各组肿瘤组织细胞周期改变；免疫组织化学法检测肿瘤组织细胞周期蛋白CyclinD1表达；TUNEL法检测肿瘤组织细胞凋亡.结果 各组瘤重较对照组减小,抑瘤率分别为39.16％、18.73％和57.04％ （F=13.566,P＜0.05）.流式细胞仪检测联合组肿瘤细胞G0/G1及G2/M期增多,S期减少,较单纯照射组差异有统计学意义（t=-6.654、-16.738、12.871,P＜0.05）.免疫组织化学法检测联合组肿瘤组织细胞周期蛋白CyclinD1表达下降；TUNEL法检测联合组肿瘤组织出现凋亡细胞.结论 IGF-1R抑制剂AG1024能增加食管癌移植瘤的放射敏感性,改变细胞周期、诱导凋亡可能是其机制之一.Objective To investigate the effect of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts and the underlying mechanisms.Methods The mouse model was established by injecting EC9706 cells subcutaneous in nude mice.When the tumors were 100 mm3 in size,the mice were divided into 4 groups randomly withcontrol group with no treatment; irradiation group with 8 Gy 6 MV Xrays at 1 and 8 d each time; AG1024-treatment group with 30 μg/（kg-d） AG1024 injected intraperitoneally （ip） 5 times a week for two weeks ; combination group：receiving both 30 μg/（kg· d）-1 AG1024 ip and irradiation of 8 Gy X-rays.The diameters of the tumors were measured every 3 days.The mice were sacrificed and the weights of tumors were measured at 15 d after treatment.Tumor inhibition rate was calculated.The cell cycle was examined by flow cytometry.The expression of cell cycle protein D1 （CyclinDl） of the tumors were detected by immunohistochemical staining.Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling （TUNEL） assay was used to detect the cell apoptosis in the tumor tissue.Results The tumor weight in the irradiation group,AG1024-treatment group and combination group were significantly decreased compared with the control group,and the inhibition rate were 39.16%,18.73%,57.04%,respectively （F =13.566,P 〈 0.05）.After treatment with AG1024 and irradiation,tumor tissue cells were significantly accumulatedin the G0/G1 and G2/M phases and decreased in S phase compared to the irradiation group （t =-6.654,-16.738,12.871,P 〈 0.05）.The CyclinD1 expression of the combination group was significantly decreased compared with the control group.In the combination group,the apoptotic cells were detected by TUNEL assay.Conclusions IGF-1R inhibitor AG1024 could change the cell cycle and induce cell apoptosis,which might result in the enhancement of radiosensitivity on the esophageal cancer xenografts.

关 键 词：食管癌 胰岛素样生长因子1受体 放疗增敏 

分 类 号：R735[医药卫生—肿瘤]