裸鼠人异位移植胃癌肝转移和腹膜转移模型的实验研究

摘要

目的：建立稳定的人裸鼠异位移植胃癌肝转移和腹膜转移模型。方法采用异位移植技术，将MKN-45和TMK-1胃癌细胞接种于裸鼠脾脏被膜和腹腔内，建立肝转移模型及腹膜转移模型。制模3周或6周分别观察异位移植转移模型的成瘤率、侵袭与转移程度、组织形态学特征。结果 MKN-45和TMK-1胃癌细胞建立的异位移植模型成瘤率皆为100％（40/40）。异位移植胃癌肝转移模型中，发现区域淋巴结肿大或转移（2/20；10％），血性腹水（3/20；15％）；异位移植胃癌腹膜转移模型中，发现血性腹水（4/20；20％），肺转移（5/20；25％）；MKN-45和TMK-1胃癌细胞经脾肝转移制模3周组肝转移评分明显低于制模6周组，差异有显著性意义（均为P＜0．01）；MKN-45和TMK-1胃癌细胞注入腹腔制模3周组腹膜转移结节数明显少于制模6周组（均为P＜0．01）；两组模型的不同种类胃癌细胞株之间的局部和远处转移率无明显相关性（r＝0．251，P＞0．05）。组织病理学观察结果证实转移癌细胞形态特征与原发胃癌细胞相似。结论裸鼠胃癌异位移植模型为研究胃癌肝转移和腹膜转移的生物学机制和抗转移治疗提供了理想的实验动物模型。%Objective To establish a feasible and stable severe combined immunodeficient nude mouse model for liver and peritoneal metastasis of human gastric cancer .Methods MKN-45 and TMK-1 human gastric cancer cells were implanted ectopically into the spleen capsules and abdominal cavity of nude mice , establishing models of liver metastasis and perito-neal metastasis in nude mice.Tumorgenicity, invasion, metastasis, and morphological characteristics of the implanted tumors were studied after post -implantation 3 weeks or 6 weeks via optical microscopy .Results 100% tumor take rates were observed in ectopic implantation nude mouse groups by either MKN -45 or TMK-1 human gastric cancer cells (60/60).The ectopic implantation groups of liver metastasis showed: metastasis of regional lymph nodes (2/20;10%) and bloody ascites (3/20;15%).The ectopic implantation of peritoneal metastasis models also exhibited:bloody ascites (4/20;20%) and metastasis of lung (5/20;25%).MKN-45 and TMK-1 human gastric cancer cells were implanted into the spleen of liver metastasis models in after 3 weeks of the injection group were less than after 6 weeks of the injection group (P<0.01).MKN-45 and TMK-1 human gastric cancer cells were implanted into the abdominal cavity of perito-neal models in after 3 weeks of the injection group were the least , and those in the remaining 6 weeks group (P<0.01). The frequency of local and distant metastasis were without correlation with the different kinds of two group (r=0.251,P>0.05).The metastasized cancer cells in metastatic lymph nodes , metastatic hepatic nodes, and metastatic peritoneal nodes showed high similarity to original primary human gastric cancer cells with histopathological features .Conclusion The liver metastasis and peritoneal metastasis models of human gastric cancer in nude mice via ectopic implantation are technically feasible and reproducible for researches on metastatic mechanism and therapeutic development of human gastric cancer .