丙氨瑞林对人子宫内膜癌裸鼠皮下移植瘤生长的作用及对DEDD表达的影响  

Effects of Alarelin on Human Endometrial Carcinoma Xenografts in Nude Mice and the Expression of DEDD

作　　者：王美婷[1] 张三元[1] 张杏林[1] 

机构地区：[1]山西医科大学第一医院妇产科,太原030001

出　　处：《国际妇产科学杂志》2015年第3期277-280,共4页Journal of International Obstetrics and Gynecology

基　　金：山西省科技攻关项目(20120313019-3)

摘　　要：目的:评价丙氨瑞林对人子宫内膜癌HEC-1-B细胞裸鼠移植瘤的作用及机制。方法:建立人子宫内膜癌裸鼠移植瘤模型,裸鼠皮下接种HEC-1-B细胞,成瘤后,根据裸鼠体积进行区组随机化分组,共分成4组(各8只),即阴性对照组(生理盐水0.2 m L/只)、丙氨瑞林低(20μg/kg)、中(40μg/kg)、高(80μg/kg)剂量组。各组给药期间测定肿瘤体积,绘制肿瘤生长曲线;用药结束后处死裸鼠,将瘤体完整取出,测瘤体积,计算抑瘤率,比较各组移植瘤体积的差异;利用苏木素-伊红(HE)染色观察肿瘤形态学变化,免疫组织化学检测肿瘤死亡效应结构域蛋白(DEDD)表达情况。结果:肿瘤生长曲线表明,阴性对照组及丙氨瑞林低、中、高剂量组的肿瘤生长速度依次减慢;丙氨瑞林低、中、高剂量组的抑瘤率分别为12.65%、27.38%和35.43%,组间多重比较差异均有统计学意义(均P<0.05);HE染色表明,阴性对照组瘤细胞排列密集,有明显异型性,细胞核大深染,核分裂相较多,间质较少,而丙氨瑞林各剂量组瘤体细胞形态各异,细胞排列较稀疏,可见大片无结构坏死区,瘤细胞核深染、固缩较多,核分裂相较少。免疫组织化学结果显示:丙氨瑞林低、中、高剂量组DEDD蛋白表达灰度值分别为156.20±5.10、142.85±7.27和113.65±4.38,均明显低于对照组的171.75±8.21,差异均有统计学意义(P<0.001)。结论:丙氨瑞林可抑制肿瘤生长,且呈一定的剂量依赖性,其机制可能与上调DEDD蛋白的表达有关。Objective：To evaluate Alarelin on human endometrial carcinoma HEC-1-B cells in nude mice and its mechanism. Methods：Establishment of endometrial carcinoma xenografts in nude mice,according to the nude volume,32 nude mice were randomly divided into 4 groups（n=8）：control group, Alarelin groups（20,40,80 μg/kg,respectively）. The growth curves of xenografts in nude mice were drawn and inhibition rates were measured. The morphological features were detected by hematoxylin and eosinstaining. The protein expression levels of DEDD were measured by immunohisto chemistry. Results：The growth curve showed that tumor volume in nude mice treated with Alarelin was smaller than that of control group. The rate of tumor inhibition in low,medium and high-dose Alarelin group were 12.65%,27.38% and 35.43%,all with a statistically significant difference（P〈0.05）. HE staining showed that tumor cells arranged in dense,with clear atypia,large nuclei,stained emitotic more,less interstitial in control group. Compared with control group,tumor cell morphology,cell arrangement sparse,showing large unstructured necrosis,tumor cell nuclei stained pyknotic more mitotic less in different dose group. Results of immunohistochemical showed that in the gray values of DEDD protein expression in low,medium and high dose groups were156.20±5.10,142.85±7.27 and 113.65±4.38 respectively,they were significantly lower than the control group（171.75±8.21,all P〈0.001）. Conclusions：Alarelin can effectively inhibit the growth of tumor,the mechanism may be correlated with increasing expressions of DEDD.

关 键 词：子宫内膜肿瘤 促性腺素释放激素 肿瘤移植 小鼠 裸 

分 类 号：R737.33[医药卫生—肿瘤]