大鼠胰腺癌CHK_1和PLK_1表达及曲古霉素A的干预作用  

Expression of checkpoint kinase 1(CHK_1) and polo-like kinase 1(PLK_1) and its intervenient effects of trichostatin A(TSA) in pancreatic cancer of SD rats

作　　者：杨乐平[1] 杨竹林[1] 李清龙[1] 谭兴国[1] 苗雄鹰[1] 

机构地区：[1]中南大学湘雅第二医院肝胆疾病研究室,湖南长沙410011

出　　处：《肝胆胰外科杂志》2011年第1期11-14,共4页Journal of Hepatopancreatobiliary Surgery

摘　　要：目的建立SD大鼠胰腺癌模型,研究胰腺癌和非癌胰腺组织中细胞周期检测点激酶1(CHK1)和polo样激酶1(PLK1)表达水平及其意义。方法实验动物随机分成3组:胰腺癌模型组(A组),曲古霉素A(TSA)干预组(B组)和对照组(C组),将二甲基苯荓蒽(DMBA)直接置入胰腺实质内(A组+B组),B组每周腹腔注射TSA 1μg,A组和B组鼠3～5个月处死,对照组(C组)于第5个月处死;肉眼检查和镜下观察胰腺癌发生情况;CHK1和PLK1染色方法均为EnVisionTM免疫组化法。结果 (1)A组3～5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌和1例为纤维肉瘤;B组3～5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌和1例为纤维肉瘤;A组肿块最大径均值大于B组(P<0.05);C组胰腺和3组胰腺外主要脏器无明显病理改变。(2)A组或B组胰腺导管癌CHK1表达阳性率与A组或B组非癌胰腺组织比较无明显差异(P>0.05);A组或B组胰腺导管癌PLK1表达阳性率明显高于A组或B组非癌胰腺组织(P<0.01);PLK1表达阳性的非癌胰腺组织导管上皮均呈不典型增生;C组胰腺CHK1和PLK1均阴性表达,2例纤维肉瘤CHK1和PLK1均阳性表达;CHK1和PLK1表达与胰腺导管腺癌分化程度、肿块大小等均无明显关系(P>0.05)。结论较大剂量DMBA置入胰实质内可在短期获得较高胰腺癌发生率,TSA能抑制胰腺癌的发生和生长;CHK1在DMBA和(或)PLK1诱导胰腺癌发生过程中可能起较重要作用。Objective To establish a model of pancreatic cancer induced by 7,12-dimethylbenzathracene（DMBA） in SD rats,and detect the expression levels of CHK1 and PLK1 and the effect of TSA on carcinogenesis of rat pancreas.Methods Experimental rats divided into three groups： group A（model group）,group B（TSA intervenient group） and group C（control group）.DMBA was directly implanted into the parenchyma of rat pancreas（group A＋group B）.The rats of group B were treated with 1 ml TSA saline solution（1μg/ml） via ip weekly.The carcinogenesis of rats executed within 3～5 months in group A and group B was observed by macrograph and under microscopy.Meanwhile,the rats in the group C were executed in 5 months.The EnVisionTM immunohistochemistry for assaying the expression levels of CHK1 and PLK1 was used in convenional paraffin-embedded sections from above pancreatic specimens.Results（1）The incidence of pancreatic cancer of group A within 3～5 months was 48.7%（18/37）,including 17 cases of ductal adenocarcinoma and 1 case of fibrosarcoma.The incidence of pancreatic cancer of group B within 3～5 months was 33.3%（12/36）,including 11 cases of ductal adenocarcinoma and 1 cases of fibrosarcoma.The mean maximal diameter of mass was significantly higher in group A than that in group B（P0.05）.No pathological changes were found in pancreas of group C and other main organs of group A＋group B.（2）No statistical differences in the positive rate of CHK1 were found between in ductal adenomcarcinoma and non-cancerous pancreatic tissues of graoup A or group B（P0.05）.The positive rate of PLK1 was significantly higher in ductal adenocarcinoma of group A or group B than those in non-cacerous pancreatic tissues of group A or group B（P0.01）.The positive expressive tissues of PLK1 in non-cancerous pancreatic tissues showed atypical hyperplasia of ductal epithelia.The pancreas of group C showed the negative expression of CHK1 and PLK1,2 cases of fibrosarcoma showed the positive expression of CHK1

关 键 词：胰腺肿瘤 Sprague-Dawely大鼠 动物模型 细胞周期检测点激酶1 POLO样激酶1 

分 类 号：R735.9[医药卫生—肿瘤]