人源性肝癌细胞小鼠原位移植瘤模型的建立及特点的比较研究  

Establishment of mouse orthotopic transplantation tumor models of human hepatoma and comparison of their characteristics

作　　者：尹君[1,2] 李景丁莎 左从林 张惠铭 佘锐萍 YIN Jun;LIJING Dingsha;ZUO Conglin;ZHANG Huiming;SHE Ruiping(College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;JOINN Laboratories(China) CO. ,LTD, Beijing 100176)

机构地区：[1]中国农业大学动物医学院,北京100193 [2]北京昭衍新药研究中心股份有限公司,北京100176

出　　处：《中国比较医学杂志》2018年第12期68-74,共7页Chinese Journal of Comparative Medicine

基　　金：G20工程龙头企业培育项目(Z141100005314003)

摘　　要：目的选择3株人源性肝癌细胞,原位接种于4种不同免疫功能缺陷的小鼠肝组织内,建立人源性肝癌细胞原位移植瘤模型并进行比较。方法将人Hep G2、HUH-7和QGY-7703细胞悬液,分别接种于不同免疫功能缺陷的小鼠(BALB/c裸鼠、NOD SCID小鼠、NOG小鼠和NPG小鼠)肝组织内。最终统计模型小鼠死亡时间、死亡率、肝重量,应用B超以及组织学检查等方法,分析比较不同免疫功能缺陷小鼠肝癌模型的特点。结果 B超和大体解剖观察结果显示各实验组小鼠均可见肝组织内有肿瘤结节形成;肝接种Hep G2细胞悬液的各组动物于实验20 d左右全部死亡,NOG和NPG小鼠生存时间显著低于BALB/c裸鼠和NOD SCID小鼠(P <0. 001); HUH-7和QGY-7703接种肝的各实验组动物分别于实验第92天和104天进行解剖,发现NOG和NPG模型小鼠肝体积显著增大并形成巨大肿瘤团块,而BALB/c裸鼠和NOD SCID小鼠仅可见肝组织出现较小的肿瘤结节; HUH-7及QGY-7703接种肝的NOG和NPG小鼠肝重量显著高于BALB/c裸鼠和NOD SCID小鼠(P <0. 05);组织学检查可见各组动物肝组织内均出现肿瘤细胞生长伴大面积坏死,部分动物肺组织发生肿瘤细胞转移。结论与BALB/c裸鼠和NOD SCID小鼠比较,肝癌细胞在NOG和NPG小鼠肝组织内生长更为迅速,最终表现为生存期短,肝体积大,重量增加。NOG和NPG小鼠可以在较短时间内完成人源性肝癌细胞的恶性增殖,缩短模型研究周期,因此NOG和NPG小鼠人源性肝细胞原位移植瘤是抗肝癌药物的研发的较为理想的模型。Objective Three human hepatoma cell lines were injected into liver tissue of four mice with different immune function defects to establish orthotopic xenograft models of human hepatoma for comparison.Methods Human HepG2,HUH-7,and QGY-7703cell suspensions were injected into the livers of mice with different immune function defects[BALB/c nude,non-obese diabetic(NOD)SCID,NOG(NOD.Cg-PrkdcscidII2rgtm1Sug/JicCrl),and NPG mice].Survival time,mortality,liver weight,B-mode ultrasound,and histology were used to analyze and compare the characteristics of liver cancer models in the various immunodeficient mice.Results B-ultrasonography and gross anatomical observations indicated that all experimental animals showed tumor nodule formation in liver tissue.Moreover,all animals injected with a HepG2cell suspension into the liver died at about20days.The survival time of NOG and NPG mice was significantly shorter than that of BALB/c and NOD SCID mice(P<0.001).Experimental groups with injected HUH-7and QGY-7703cell suspensions into the liver were autopsied at day92and104,respectively.The liver volumes of NOG and NPG model mice were increased significantly and formed large tumor masses,whereas BALB/c nude and NOD SCID mice showed only small tumor nodules in liver tissues.The weights of NOG and NPG mouse livers were significantly higher than those of BALB/c nude and NOD SCID mouse livers(P<0.05).Histological examination showed that all groups of animals exhibited tumor cell growth with large areas of necrosis and some animal lung tissues had tumor metastasis.Conclusions Compared with BALB/c nude and NOD SCID mice,hepatoma cells grow more rapidly in the liver tissues of NOG and NPG mice,and the survival time is short,the liver volume is large,and the weight is increased.The human hepatoma cell lines can complete malignant proliferation in NOG and NPG mice in a short time for time-efficient model study.Therefore,human-derived hepatocyte xenografts in NOG and NPG mice are an ideal model for the development of anti-hepatoma drugs.

关 键 词：原位移植癌 肝癌 动物模型 NOG小鼠 

分 类 号：R-33[医药卫生]