目的:建立SD大鼠胰腺癌模型,研究细胞连接调控蛋白(Claudin-1,Occludin,E-cad,Snail)在胰腺癌发生发展过程中的作用及其意义.方法:90只大鼠随机分为二甲基苯荓蒽(DMBA)组(A组,n=40),DMBA+曲古霉素A(TSA)组(B组,n=40)和空白对照组(C组,n=10只).将DMBA直接置入A,B组胰腺实质内建立胰腺癌模型,B组腹腔注射TSA,～5 mo内处死并观察胰腺癌发生情况,C组于第5 mo处死.采用EnVision~(TM)免疫组化法检测Claudin-l,Occludin,E-cad,Snail的表达.结果:A组3～5 mo癌发生率为48.6%(18/37),5 mo(60.0%)高于4 mo组(40.0%)和3 no组(28.6%).B组3～5 mo癌发生率为33.3%(12/36),5 mo(40.0%)高于4 mo组(30.0%)和3 mo组(16.7%).A组发癌率高于B组.A组,B组胰腺导管癌分别为17例和11例,其余为纤维肉瘤;A组胰腺癌最大径均值大于B组(A组:0.5-1.0 em 7例,1.0～2.0em 10例,>2.0 cm 1例;B组:0.5～1.0 cm 9例,1.0～2.0 cm2例,>2.0 em 1例,P<0.05);C组胰腺和A,B,C组胰腺外主要脏器均未见明显病理改变.A组+B组胰腺导管癌Claudin-1,Occludin,E-cad表达阳性率明显低于A组+B组非癌胰腺组织(P<0.05或P<0.01),但Snail则相反(P<0.01);在胰腺导管腺癌中Claudin-1,Occludin,E-cad表达均相互呈一致性(P<0.05或P<0.01),但二者均与Snail表达呈明显不一致性(P<0.05或P<0.01).结论:较大剂量DMBA置入胰实质内可在短期内获得较高的SD鼠胰腺癌发生率,TSA能抑制胰腺癌发生和生长;Claudin-1,Octludin,E-cad和Snail在DMBA诱导sD大鼠胰腺癌发生中可能有重要作用.
Expression of regulated proteins of cell junctions and their significance on the carcinogenesis of Sprague-Dawely(SD) rat pancreas
AIM: To establish a model of pancreatic cancer in Sprague-Dawely(SD) rats, and to detect the expression of regulated proteins in cell junctions(Claudin-1, Occludin, E-cad, Snail) and their significances on the carcinogenesis in rats pancreas. METHODS: Ninety rats were randomly divided into A( n =40) , B(ra=40) and C(ra = 10) groups. For group A and B, dimethyl-benzathracene, ( DMBA) was directly implanted into the parenchyma of rat pancreas to establish pancreatic cancer model. The rats of group B were treated with trichostatin A(TSA) via intraperitoneal weekly. The rats in group C served as the controls. The rats were executed within 3-5 months, and the carcinogenesis of the rats was observed by pathological methods. The Envision~(TM)immunohis-tochemistry for assaying the expressive levels of Claudin-1, Occludin, E-cad and Snail was used in conventional paraffin-embedded sections from above pancreatic specimens. RESULTS; The incidence of pancreatic cancer in group A within 3-5 months was 48.6% (18/37), 28.6% (2/7) at 3 months, 40.0% (4/10) at4 months and 60. 0% ( 12/20) at 5 months. And that in group B was 33.3%(12/36), 16.7%(l/6), 30.0%(3/10) and 40.0%(8/ 20) ,respectively. The prevalence rate in group A was higher than that of group B. Cases of pancreatic ductal adenocarcinoma in group A and B respectively were 17 and 11, and others were fibro-sarcoma. The maximal diameter of tumor mass in group A were significantly larger than those in group B( group A; 0. 5 -1.0 cm 7 cases, 1.0 -2.0 cm 10 cases, >2.0 cm 1 case vs group B: 0.5 -1.0 cm 9 cases, 1. 0 - 2. 0 cm 2 cases, > 2. 0 cm 1 case, P < 0.05). No pathological changes were found in pancreas of group C and other main organs of group A, B and C. The positive rates of Claudin-1 , Occludin and E-cad were significantly lower in ductal adenocarcinoma of group A + group B than those in non-cancerous pancreatic tissues of group A + group B ( P < 0. 05 or P < 0.01) ; but Snail was opposite( P <0. 01). The consistencies were found among the expressive levels of clanudin-1, Occluding and E-cad in ductal adenocarcinoma of pancreas (P <0.05 or P <0.01). Also the inconsistence was found among the expressive levels of Snail and the expressive levels of Claudin-1, Occludin or E-cad in ductal adenocarcinoma of pancreas ( P < 0. 05 or P < 0. 01 ). CONCLUSION: Direct implantation of DMBA into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. TSA may have an inhibitive effect on carcinogenesis and growth. The regulated proteins of cell junctions ( Claudin-1, Occludin, E-cad and Snail) might have important effects on carcinogenesis induced by DMBA in rat pancreas.
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万方数据
维普
