靶向抑制胰岛素样生长因子Ⅰ型受体对裸鼠恶性胸腔积液的治疗作用  

Therapeutic effect of IGF-1R.targeting inhibitor （TAE226） on malignant pleural effusion in nude mice

作　　者：张巍[1] 吴杨[1] 龚玲[1] 朱红兰[1] 黄贵川[1] 周国旗[1] 吴凯峰[2] 刘代顺[1] 

机构地区：[1]遵义市第一人民医院呼吸内科,563000 [2]遵义市第一人民医院检验科,563000

出　　处：《中华肿瘤杂志》2016年第8期565-571,共7页Chinese Journal of Oncology

基　　金：国家自然科学基金(81360350)；贵州省科技厅社发公关基金(黔科合 SY字[2012]3102号)；贵州省科技创新人才团队建设项目(黔科合人才团队[2015]4018号)；遵义市科技计划项目(遵市科合社字[2012]6号)Fund programNational Natural Science Foundation of China (81360350)；Social Development Key Projects of Guizhou Department of Science and Technology ( Qiankehe SY Zi [2012]3102)；Science and Technology Innovation Talent Team Construction Projects of Guizhou(Qiankeherencaituan dui[2015]4018)；Zunyi Plan of Science and Technology

摘　　要：目的 探讨靶向抑制胰岛素样生长因子Ⅰ型受体（IGF-1R）对裸鼠恶性胸腔积液的治疗作用。方法 Bal B/c裸鼠胸膜腔内注射人肺腺癌A549细胞，构建裸鼠正位恶性胸腔积液模型。将裸鼠随机分为模型组和TAE226治疗组，分别经口灌胃双蒸水和TAE226（20 mg/kg），观察两组裸鼠的胸腔积液、肿瘤重量。采用HE染色观察肿瘤组织学改变，酶联免疫吸附试验（ELISA）法检测胸水上清液IGF-1R蛋白的表达，逆转录聚合酶链反应（RT-PCR）检测肿瘤组织中IGF-1R mRNA的表达，免疫组化法检测肿瘤微血管密度（MVD）和细胞增殖指数（PI），Western blot法检测肿瘤组织中IGF-1R、p-IGF-1R、PI3K和p-PI3K蛋白的表达。结果 模型组和TAE226治疗组裸鼠胸腔积液分别为（241.4＋89.7）μl和（121.7＋78.8）μl，差异有统计学意义（P〈0.05）。模型组和TAE226治疗组的肿瘤重量分别为（671.4±281.4）mg和（316.7±186.3）mg，差异有统计学意义（P〈0.05）。RT-PCR检测显示，TAE226治疗组的IGF-1R mRNA表达水平为0.914＋0.029，模型组的IGF-1R mRNA表达水平为1.152±0.037，差异有统计学意义（P〈0.01）。ELISA检测结果显示，模型组和TAE226治疗组胸腔积液中IGF-1R蛋白表达水平分别为（41.0±4.7）μg/L和（24.0±3.1）μg/L，差异有统计学意义（P〈0.01）。免疫组化检测显示，模型组和TAE226治疗组的微血管密度（MVD）分别为（34.75±3.49）个/mm2和（22.25±3.63）个/mm2，PI分别为（75.25±7.15）%和（45.75±5.12）%，差异均有统计学意义（均P〈0.01）。Western blot检测显示，模型组中IGF-1R和PI3K蛋白的表达水平分别为1.03±0.33和1.05±0.28，TAE226治疗组分别为0.98±0.37和0.98±0.19，差异无统计学意义（P〉0.05）；模型组中p-IGF-1R和p-PI3K蛋白的表达水平分别为1.08±0.10和1.12±0.09，TAE226治疗组分别为0.51±0.08和0.86±0.09，差异有统计学意义（P〈0.01）。结论 抑制IGF-Objective To study the therapeutic effect of IGF-1R inhibitor TAE226 on malignant pleural effusion （MPE） in nude mice. Methods Human lung carcinoma A549 cells were injected into the pleural cavity of nude mice to establish MPE model. The mice were randomly divided into model group and treatment group, and were orally administered with distilled water and TAE226 （20 mg/kg） in the same volume, respectively. The volume of pleural effusion and tumor weight of the two groups were observed. HE staining was used to reveal the histological changes and enzyme-linked immunosorbent assay （ELISA） was used to detect the IGF-1R protein expression. IGF-1R mRNA level in the tumor tissue was determined by RT-PCR. Microvessel density （MVD） and cell proliferation index （PI） were assessed by immunohistochemical analysis. The protein expression levels of IGF-IR, p-IGF-IR, PI3K and p-PI3K in the tumor tissue were determined by Western blotting. Results The volumes of pleural effusion were （241.4 ± 89.7 ） μl and （ 121.7 ± 78.8） μl in the model and treatment groups, respectively （P〈0.05）. The tumor weight of treatment group was （316.7±186.3） mg, significantly lower than that of the model group （671.4±281.4） mg （P〈 0.05）. RT-PCR analysis showed that IGF-1R mRNA level was 0.914± 0.029 in the treatment group, significantly lower than that of the model group （ 1.152±0.037, P〈0.01 ）. The ELISA data revealed that IGF-1R protein expression level of the model group was significantly higher than that of the treatment group [ （41.0±4.7） μg/L vs. （24.0±3.1） μg/L, P〈0.01 ]. Immunohistochemical analysis showed that there were significant differences between MVD and PI in the model and treatment groups [ MVD, 34.75 ± 3.49 vs. 22.25±3.63; PI, （75.25±7.15）% vs. （45.75±5.12）%;P〈0.01 for both）. Western blot data showed that IGF-1R and PI3K protein expression levels were not significantly different between the model and treatment groups （1.03±0.33 vs. 0.98±0.37

关 键 词：胸腔积液 恶性 胰岛素样生长因子Ⅰ型受体 TAE226 肿瘤侵袭 小鼠 裸 

分 类 号：R730.5[医药卫生—肿瘤]