小鼠胰腺癌肝转移模型及相关分子表达的研究  

Experimental animal models of pancreatic carcinogenesis and liver metastasis and metastasis-related molecules

作　　者：刘玉美 李婷 杨秀疆 Yumei Liu;Ting Li;Xiujiang Yang(Tumor Research Institute,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Department of Endoscopy)

机构地区：[1]复旦大学附属肿瘤医院内窥镜中心,复旦大学上海医学院肿瘤学系,上海市200032 [2]复旦大学肿瘤研究所

出　　处：《中国肿瘤临床》2019年第11期551-556,共6页Chinese Journal of Clinical Oncology

摘　　要：目的:经脾注射法建立小鼠胰腺癌肝转移模型,初步研究部分转移相关分子的基因表达水平变化。方法:用脾脏注射法在12只C57/BL6小鼠中建立胰腺癌肝转移模型,6只小鼠注射PBS缓冲液作为对照。术后4周处死并解剖小鼠,观察腹腔内转移情况和肝脏成瘤的情况。采用实时荧光定量PCR检测小鼠脾脏胰腺癌组织、胰腺癌肝转移组织及肝转移灶旁肝组织中相关转移分子的基因表达情况,比较其差异。结果:实验组12只小鼠的肝脏转移率为83.33%,解剖后观察脾脏表面均见单一瘤结节,其中10只小鼠肝脏表面及切面见多发散在的转移瘤结节,肝脏成瘤率83.33%,肝脏瘤组织细胞形态学符合胰腺癌的特征。在构建成功的10只胰腺癌肝转移小鼠模型中,CCL-17、CCL-22、CD44等分子在脾脏癌灶与肝转移灶的基因表达量高于癌旁肝组织,相对表达率<1(P<0.05);Ang-2、BAK、BAX等分子在脾脏癌灶与肝转移灶的基因表达量低于癌旁肝组织相对表达率>1<1(P<0.05)。结论:经脾注射法成功建立小鼠胰腺癌肝转移模型,能较好模拟胰腺癌体内肝转移过程。小鼠胰腺癌肝转移模型中相关转移分子基因表达水平的变化趋势与人体内胰腺癌肝转移基本一致,可为筛选抗肿瘤药物和研究胰腺癌转移行为提供帮助。Objective:To develop a reliable model of pancreatic carcinogenesis and liver metastasis in mice and preliminarily analyze metastasis-related molecules.Methods:Liver metastasis models of pancreatic cancer were made by injecting murine Panc-2 cells in the spleens of 12 C57/BL6 mice.Six mice in the control group were injected with phosphate buffered saline.Liver metastases were detected pathologically in the experimental group.Quantitative real-time PCR was used to analyze the variation in the expression levels of metastasis-related molecules in the tumor tissue located in the spleen,metastatic tumor tissues in the liver,and liver tissue adjacent to metastatic carcinoma.Results:In the experimental group,the incidence rate of liver metastasis was 83.33%.An anatomical study showed that there was a single giant tumor nodule at every injection site in the spleen,while multiple nodular metastases appeared in the livers of 10 mice,with the liver tumorigenesis rate 83.33%.The pathological results indicated that the tumor cell pattern of liver metastasis was in accordance with pancreatic adenocarcinoma.CCL-17,CCL-22,CD44,and other molecules had higher impression levels in the metastatic tumor tissues in the liver and the tumor tissue of spleen than in the liver tissue adjacent to metastatic carcinoma.Expression levels of Ang-2,BAK,BAX,and other molecules were higher in the liver tissue adjacent to metastatic carcinoma,and the relative expression level of gene was more than 1(P<0.05).Conclusions:Intrasplenic injection of pancreatic cancer cells successfully developed a model of liver metastasis that partly mimicked the natural metastatic process,which showed variations in the expression levels of metastasis-related molecules similar to that in the human body.This is a reliable method to produce pancreatic cancer liver metastasis in mice and may be valuable in experimental studies for screening anti-tumor durgs.

关 键 词：胰腺癌 经脾注射法 转移 实时定量PCR 分子 表达 

分 类 号：R735.9[医药卫生—肿瘤] R-332[医药卫生—临床医学]