丙氨瑞林对人子宫内膜癌细胞裸鼠皮下移植瘤生长的影响及机制研究  

Effection and mechanism of alarelin on human endometrial carcinoma in nude mice of subcutaneous Xenograft

作　　者：张杏林[1] 张三元[1] 苏焕成 

机构地区：[1]山西医科大学第一临床医学院妇产科,太原030001

出　　处：《中华临床医师杂志（电子版）》2013年第6期139-142,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：山西省科技攻关项目:恶性肿瘤发病机制及生物治疗的研究GnRH-A对TGF-β1/Smads介导人子宫内膜癌裸鼠移植瘤目的基因表达的影响(20120313019-3)

摘　　要：目的探讨不同剂量的醋酸丙氨瑞林对人子宫内膜癌裸鼠皮下移植瘤生长及其可能的作用机制。方法建立子宫内膜癌裸鼠移植瘤模型,选32只雌性荷瘤裸鼠随机分为4组,即空白对照组、醋酸丙氨瑞林干预组(20μg/kg、40μg/kg、80μg/kg),不同剂量醋酸丙氨瑞林组均采取肌肉注射方式连续给药,4周后处死裸鼠,将移植瘤完整取出,测量肿瘤体积、绘制肿瘤生长曲线、计算抑瘤率,并应用免疫组织化学法检测瘤组织中TGF-β1、Smad2/3、Smad7蛋白的表达。结果实验对照组、低、中、高剂量醋酸丙氨瑞林组中移植瘤生长曲线斜率依次减小,生长速度依次减慢。低、中、高剂量醋酸丙氨瑞林抑瘤率分别为(13.03±5.4)%、(26.42±7.3)%、(43.27±6.9)%,组间两两比较差异有统计学意义(P<0.05)。随着醋酸丙氨瑞林浓度的升高,各干预组TGF-β1、Smad2/3蛋白表达水平明显升高,Smad7蛋白表达水平明显下降,且与对照组相比,差异有统计学意义(P<0.05)。结论醋酸丙氨瑞林对子宫内膜癌细胞株Hec-1-B裸鼠皮下移植瘤生长有抑制作用,且呈一定的剂量依赖效应,其作用机制可能与调节TGF-β1/Smads信号转导通路有关。Objective To investigate the effects and its possible molecular mechanisms of different doses of alarelin on human endometrial carcinoma in nude mice of subcutaneous xenograft.Methods Human endometrial carcinoma models were established by subcutaneous transplantation in nude mice,and then 32 of the mice were randomly divided into 4 groups：control group,alarehn groups （20,40,80 μg/kg,respectively）.The different-dose Alarelin were injected into the kinds of mice of groups and the blank control group were injected with the isodose isotonic Na chloride in the same way.The systemic condition of the mice were observed for 4 weeks,then the tumor were removed completely.We measured the size of tumor,drawed the growth curve,calculated the inhibition rate of the tumor,then,etected the expression of the TGF-β1,Smad2/3,Smad7 with the immunohistochemical technology.Results The slop of tumor growth curve decreased gradually form control group to high dose of alarelin group,that means growth rate was slowly by and by.Alarelin 20,40,80 μg/kg respectively inhibited tumor growth by（13.03 ±5.4） ％,（26.42 ± 7.3） ％,（43.27 ± 6.9） ％.The difference was significant （P ＜ 0.05,respectively）.The immunohistochemical results showed that the expression of TGF-β1,Smad2/3 rised obviously in treated groups with the increasing dose of Alarelin,inversely,the expression of Smad7 reduced obviously,and the difference of the treated groups was significant （P ＜ 0.05,respectively）.Conclusions Alarelin might inhibit directly the growth of the human endometrial carcinoma in nude mice of subcutaneous xenograft and the effect was dose-dependent,and it may be related to adjust TGF-β1/Smads signal transduction pathways.

关 键 词：子宫内膜肿瘤 受体 LHRH 转化生长因子β1 SMAD蛋白质类 移植瘤 

分 类 号：R737.33[医药卫生—肿瘤]