曲古霉素A抑制SD大鼠胰腺癌的发生及其分子机制的探讨  

Inhibition effect of TSA on pancreatic cancer of SD rats and its molecule mechanism

作　　者：谭兴国[1] 杨竹林[2] 刘洁琼[1] 杨乐平[1] 苗雄鹰[1] 

机构地区：[1]中南大学湘雅二医院肝胆疾病研究室,湖南长沙410011 [2]南大学湘雅二医院肝胆疾病研究室,湖南长沙410011

出　　处：《中华肿瘤防治杂志》2010年第1期9-13,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:建立SD大鼠胰腺癌模型,观察曲古霉素A(TSA)对二甲基苯荓蒽(DMBA)诱癌的抑制作用,探讨Ezrin、HGF和C-met表达与胰腺癌发生发展的相关性。方法:90只SD大鼠随机分为3组,DMBA置入胰腺实质内(A组+B组),B组每周腹腔注射TSA1μg;A组和B组于3～5个月内处死,对照组(C组)于第5个月处死。Ezrin、HGF和C-met染色方法均为石蜡切片EnVisionTM免疫组化法。结果:1)A组癌发生率为48.7%;B组癌发生率为33.3%;A组胰腺癌最大径均值>B组,P<0.05;C组胰腺和A、B两组胰腺外主要脏器均未见明显病理改变;2)A组+B组胰腺导管癌Ezrin、HGF和C-met阳性表达率明显高于A组+B组非癌胰腺组织,P<0.01;A组胰腺导管癌Ezrin、HGF和C-met阳性表达率明显高于A组非癌胰腺组织(P<0.05),C组胰腺和2例纤维肉瘤Ezrin、HGF和C-met均为阴性表达;Ezrin、HGF和C-met在胰腺导管癌中表达呈一致性,P<0.05。结论:较大剂量DMBA置入胰腺实质内可获得较高胰腺癌发生率;Ezrin、HGF和C-met在DMBA诱癌过程中可能有重要促癌发生作用;TSA能抑制胰腺癌发生和生长,其机制可能与抑制Ezrin、HGF和C-met表达有关。OBJECTIVE：To establish a model of pancreatic cancer in SD rats,explore the inhibition effect of TSA on carcinogenesis of DMBA,and detect the expresson levels of Ezrin,HGF and C-met and the effects on carcinogenesis of rat pancreas. METHODS：DMBA was directly implanted into the parenchyma of rat pancreas （group A＋group B）. The rats of group B were treated with 1 μg TSA,via ip,weekly. The rats were executed within 3-5 months in group A and group B,and the rats in the control （group C） were executed in 5 month. The EnvisionTM immunohistochemistry for assaying the expresson levels of Ezrin,HGF and C-met was used in paraffin-embedded sections. RESULTS：1）The incidence of pancreatic cancer in group A was 48.7% and in group B was 33.3%. The maximal diameter of mass was significantly larger in group A than that in group B （P〈0.05）. No pathological changes were found in pancreas of group C and other main organs of group A and group B. 2）The positive rates of Ezrin,HGF and C-met were significiantly higher in ductal adenocarcinoma of group A＋ group B than those in non-cancerous pancreatic tissues of group A＋group B （P〈0.01）. The positive rates of Ezrin,HGF and C-met were significantly higher in ductal adenocarcinoma of group A than those in non-cancerous pancreatic tissues of group A（P〈0.05）. The pancreas of group C and 2 cases of fibrosarcoma showed negative expression of Ezrin,HGF and C-met. The consistency were found among the expressive levels of Ezrin,HGF and C-met in ductal adenocarcinoma （P〈0.05）. CONCLUSIONS：DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence. HGF and C-met. Ezrin,HGF and C-met may have important promotive effects on carcinogenesis of pancreas. TSA may have an inhibitive effects on carcinogenesis and growth,its effects might be related to inhibite the expressive levels of Ezrin.

关 键 词：胰腺肿瘤 模型 动物 肝细胞生长因子 原癌基因蛋白质C-MET 

分 类 号：R735.9[医药卫生—肿瘤]