裸小鼠人胃癌肝转移模型的筛选和建立

Liver Metastatic Human Gastric Carcinoma Established in Nude Mice Using Orthotopic Organ Selection of Metastasis

目的通过筛选建立裸小鼠人胃癌肝靶向高转移模型。方法采用原位移植技术,将组织学完整的MKN-45肿瘤组织块移植至裸小鼠胃壁上,按照胃原位移植→肝转移→皮下扩增→胃原位移植方法进行反复筛选,观察肿瘤原位移植成瘤率、侵袭和转移及形态学特征(光镜、电镜)。结果筛选出一个裸小鼠人胃癌肝靶向高转移模型,将其命名为MKN-45sci,已传至第5代。肿瘤的原位移植成瘤率、肝转移率和腹腔淋巴结转移率皆为100%,部分动物伴发肺、脾、膈等脏器转移及血性腹水。组织病理学和电镜观察结果证明其特征与原肿瘤相似。结论建立的裸小鼠人胃癌肝转移模型完整地再现了胃癌患者的临床过程。

Objective To establish a highly liver metastatic model of human gastric carcinoma in nude mice by using orthotopic organ selection of metastasis. Methods Histologically intact MKN-45 human gastric carcinoma tissues were orthotopicly implanted into the gastric mucosa layers in nude mice, repeated screening was conducted according to the method of gastric orthotopic implantation→ liver metastasis →subcutaneously inoculation→ gastric orthotopic implantation. Tumorgenicity, invasion, metastasis and morphological characteristics of the implanted tumors were studied by light microscopy and electron microscopy. Results Highly liver metastatic models of human gastric carcinoma named MKN- 45sci were obtained after organ screen. They had been passaged in vivo for 5 generations. 100% tumor take rates were observed, the metastases of liver and lymph nodes were noted in all of the animals. They were also exhibited other features： metastasis of lung、 spleen、 diaphragm and bloody ascites. The primary and metastatic tumors were similar to the original human carcinoma in histopathological and electron microscopy features. Conclusions The orthotopic implant models of human gastric carcinoma displayed features of human clinical gastric carcinoma in animals. They provided a useful tool for the study of metastatic mechanism and treatment of human gastric carcinoma.