裸鼠胰腺癌高肝转移模型的建立

山东大学学报(医学版)

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裸鼠胰腺癌高肝转移模型的建立

崔亚洲¹，贾青²，王兆朋²，王朝霞²，田美¹，张月英²，张维东²，韩金祥¹

1．山东省医药生物技术研究中心，卫生部生物技术药物重点实验室，山东省现代医用药物与技术重点实验室，济南 250062； 2．山东省医学科学院基础医学研究所，济南 250062

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2008-08-16 发布日期:2008-08-16
通讯作者: 韩金祥

A pancreatic cancer model with high liver metastatic potential in nude mice

CUI Ya-zhou¹, JIA Qing², WANG Zhao-peng², WANG Zhao-xia², TIAN Mei¹, ZHANG Yue-ying², ZHANG Wei-dong², HAN Jin-xiang¹

1. Shandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Jinan 250062, China; 2. Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China

Received:1900-01-01 Revised:1900-01-01 Online:2008-08-16 Published:2008-08-16
Contact: HAN Jin-xiang

摘要/Abstract

摘要：

目的〓〖HTK〗建立高肝转移率的胰腺癌转移裸鼠模型，为抗胰腺癌肝转移药物的筛选和机理研究提供基础。〖HTW〗方法〓〖HTK〗人胰腺癌MIA-PaCa2细胞株脾内接种形成肝转移病灶，经反复体外原代培养和体内接种后筛选出高转移亚型MIA-PaCa2-3，MIA-PaCa2-3细胞DAPI荧光标记后尾静脉注射建立裸鼠胰腺癌模型，小动物光学分子成像系统动态观察肝脏转移肿瘤的生长变化，荧光显微镜观察肝脏肿瘤细胞转移情况。采用Western-blot的方法比较MIA-PaCa2-3细胞及其源细胞MIA-PaCa2细胞转移部分相关基因的蛋白表达水平。〖HTW〗结果〓〖HTK〗MIA-PaCa2-3细胞尾静脉注射裸鼠6～8周后，裸鼠活体肝脏区域及肝脏冰冻切片均可见明显弥漫性的荧光影像，肝脏转移率为80%（8/10），明显高于其源细胞MIA-PaCa2（2/10）；MIA-PaCa2-3细胞转移相关基因基质金属蛋白酶2（matrix metallo proteinase-2，MMP-2）、基质金属蛋白酶9（matrix metallo proteinase-9，MMP-9）、血管内皮细胞生长因子（Vascular endothelial growth factor，VEGF）表达水平明显高于MIA-PaCa2细胞。〖HTW〗结论〓〖HTK〗MIA-PaCa2-3细胞尾静脉注射可建立高肝转移率的裸鼠胰腺癌模型，借助荧光示踪可以简便、可靠地观察肝脏转移肿瘤的生长情况，适于胰腺癌肝转移机制研究和抗肝转移药物的筛选。

关键词: 裸, 肝脏, 小鼠, 肿瘤转移, 胰腺肿瘤

Abstract:

Objective〓〖WTBZ〗To establish a pancreatic cancer nude mice model with high metastatic potential for study of the mechanism and drug screening of pancreatic cancer liver metastasis. 〖WTHZ〗Methods〓〖WTBZ〗Human pancreatic cancer cell lines MIA-PaCa2 were injected into the spleen, and cancer cells from liver metastatic foli of mice were cultured in vitro and subsequently injected into the spleen. After the procedures were performed three times, a sub-line of MIA-PaCa2 with high livermetastatic potential MIA-PaCa2-3 labeled with CM-DiI were injected through the tail vein. Four metastatic related gene expressions including MMP-2, MMP-9, VEGF and bFGF were compared between MIA-PaCa2 and MIA-PaCa2-3 cells by Western-blot. 〖WTHZ〗Results〓〖WTBZ〗Pancreatic cancer models with MIA-PaCa2-3 had a significantly higher metastatic rate (8/10) than its parental cells. The expressions of MMP-2, MMP-9 and VEGF were higher in MIA-PaCa2-3 than in MIA-PaCa2. 〖WTHZ〗Conclusions〓〖WTBZ〗MIA-PaCa2-3 cells demonstrate high metastatic potentials in the liver of nude mice. This model is suitable for study of the mechanism and drug testing for pancreatic cancer metastasis.

Key words: Pancreatic Neoplasms, Neoplasm Metastasis, Liver, Mice, nude

中图分类号:

R730.1

崔亚洲,贾青,王兆朋,王朝霞,田美,张月英,张维东,韩金祥 . 裸鼠胰腺癌高肝转移模型的建立[J]. 山东大学学报(医学版), 2008, 46(8): 739-741.

CUI Ya-zhou,JIA Qing,WANG Zhao-peng,WANG Zhao-xia,TIAN Mei,ZHANG Yue-ying,ZHANG Wei-dong,HAN Jin-xiang

. A pancreatic cancer model with high liver metastatic potential in nude mice[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(8): 739-741.

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裸鼠胰腺癌高肝转移模型的建立

A pancreatic cancer model with high liver metastatic potential in nude mice

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