BNX小鼠人胃癌原位移植模型的建立及其生物学特性的观察

An establishment of orthotopic implant models for human gastric carcinoma in BNX mice and their biological properties

目的 应用T、B、NK细胞联合免疫缺陷的BNX小鼠建立人胃癌原位移植高转移模型。方法 将MKN 4 5细胞株接种至BNX小鼠皮下 ,成瘤后将肿瘤组织剪成小块通过手术移植至BNX小鼠的胃壁 ,观察肿瘤生长与转移情况 ,8周后对动物进行解剖。结果 胃壁原位移植瘤浸润破坏胃壁各层组织结构 ,并直接扩散至周围脏器。肿瘤的移植成功率为 10 0 % ( 2 3/ 2 3) ,表现出很高的侵袭和转移特性 :原位肿瘤平均体积 2 837.0 7± 10 4 4 .0 4mm3 ,局部和远处淋巴结转移率达 83% ( 19/ 2 3) ,肝转移率为 83% ( 19/ 2 3) ,肺转移率为 6 5 % ( 15 / 2 3) ,膈转移率为 39% ( 9/ 2 3) ,发生腹腔种植与腹水的动物为 35 % ( 8/ 2 3) ,此外 ,还有个别脾转移。结论 通过T、B、NK细胞联合免疫缺陷的BNX小鼠建立人胃癌原位移植模型可以更好地模拟人胃癌侵袭与转移本身的自然过程 。

Objective To establish a metastatic model of human gastric carcinoma using surgical orthotopic implant technique in the beige/nude/xid-linked immune-deficient (BNX) mice. Methods Human gastric carcinoma cell line MKN-45 was inoculated subcutaneously into BNX mice to develop growing tumors. Tumor tissue pieces were implanted to the stomach wall of BNX mice by surgical orthotopic implantation. Subsequently, we observed orthotopic tumor growth and metastasis. Tumor-bearing BNX mice underwent autopsy after eight weeks.Results Implanted tumors invaded and destroyed the normal structure of the stomach wall and infiltrated to the adjacent organs. All(23/23) of BNX mice were successfully orthotopic all implanted and exhibited extremely high invasive and metastatic ability: average tumor volume was 2837.07±1044.04mm 3 ,the metastases of local and distant lymph nodes were noted in 83%(19/23) of the animals, the rates of liver, lung and diaphragm metastases were 83%(19/23), 65%(15/23), and 39%(9/23), respectively. Peritoneal seeding with ascites were also obtained in 35%(8/23) of the animals. Conclusion Orthotopic implant models of human gastric carcinoma in BNX mice can display the pattern of invasiveness and metastasis of human clinical gastric carcinoma. They may be regarded as the more real model for further experiment as study and contribute to the development of new preventive and therapeutic strategies as well as further study of the metastatic mechanism of human gastric carcinoma.