胃癌灶原位移植腹膜转移癌裸小鼠模型的建立及生物学性状鉴定  

Establishment and identification of an orthotopic transplanted model of gastric carcinoma with peri- toneal carcinomatosis in nude mice

作　　者：刘少平[1] 张珏[1] 袁静萍[1] 王群[1] 邵丽华[1] 方敏[1] 李雁[1] 

机构地区：[1]武汉大学中南医院肿瘤科肿瘤生物学行为湖北省重点实验室湖北省肿瘤医学临床研究中心,430071

出　　处：《中华实验外科杂志》2012年第10期2082-2084,F0004,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（8117396/H1808）

摘　　要：目的建立胃癌灶原位移植腹膜转移癌裸小鼠模型，鉴定其侵袭转移生物学特点。方法取11只BALB／C裸小鼠，将人MGC-803胃癌组织原位移植于胃窦部，建立裸小鼠人胃癌灶原位移植腹膜转移癌模型。测定裸鼠体质量、血常规，并采用肿瘤组织形态学及免疫组织化学方法观察肿瘤增生、凋亡及侵袭转移相关分子标志[B淋巴细胞／白血病（bcl）-2、bcl-6、原位末端转移酶标记（TUNEL）、细胞核增殖抗原（Ki-67）、CD34、D2-40、血管内皮生长因子（VEGF）、基质金属蛋白酶（MMP）-9]。结果模型制作成功率100％（11／11），生存期内裸鼠体质量平缓增加。常规病理学检测瘤块重量为210．5—379．0mg（中位数267．5mg），癌细胞异质性明显，微血管／淋巴管中癌栓易见，可见胃周淋巴结及肝脏转移。肿瘤增殖相关分子检测显示bcl-2阳性率为0．0％～10．4％（中位数为3．3％），bcl-6阳性率为0．0％-11．1％（中位数为3．3％），Ki-67阳性率为40．5％-48．6％（中位数为45．4％），TUNEL阳性率为0．2％-3．1％（中位数为0．9％），肿瘤侵袭转移相关分子检测肿瘤组织血管标记CD34观察到1—11（中位数为3）个脉管／视野，通过淋巴管标记D2-40观察到0—5（中位数为2）个脉管／视野，分泌VEGF的阳性细胞为68．5％～95．8％（中位数82．4％），MMP-9阳性细胞数为13．5％-50．0％（中位数为23．5％）。结论成功建立胃癌灶原位移植腹膜转移癌裸小鼠模型，并表现出了低分化胃腺癌的典型生物学特点。Objective To establish an orthotopic transplanted model of gastric cancer with peritoneal carcinomatosis in nude mice and identify the pathological features of the model. Methods The homogenate of MGC-803 gastric cancer tissue was planted in gastric antrum of 11 BALB/c nude mice to establish the model of gastric cancer with peritoneal carcinomatosis. The general status was recorded. The routine morphological examination and immunohistochemistry were performed to detect tumor biological fea- tures related to proliferation, apoptosis, invasion and metastasis [ B lymphocytes/leukemia-2 （bcl-2）, bcl-6, Ki-67, TdT-mediated dUTP nick end labeling （TUNEL）, vascular endothelial growth factor （VEGF）, matrix metalloproteinase （ MMP）-9, CD34, and D2-401. Results The animal models were constructed successfully （11/11 ）. The body weight of nude mice was slowly increased during the model development. The orthotopic tumor weight was （210. 5-379.0） mg （median 267. 5 mg）. Cancer cell hetero- geneity, and microvascular/lymphatic tumor thrombus were obviously observed as well as perigastric lymph nodes and liver metastases. Tumor proliferation-related molecule detection showed that bcl-2 positive rate was 0. 0%-10. 4% （median 3.3% ）, bcl-6 positive rate was 0. 0%-11.1% （median 3. 3% ）, Ki-67 positive rate was 40. 5%-48.6% （median 45.4% ）, and TUNEL positive rate was 0. 2%-3. 1% （median 0. 9% ）. The number of tumor blood vessels marked with CD34 was 1-11 （median 3）/400 x field of vision. The number of lymphatics marked with D2-40 was 0-5 （median 2）/400 ~ field of vision. VEGF positive rate was 68.5%- 95. 8% （ median 82. 4% ）, and MMP-9 positive rate was 13.5% -50. 0% （ median 23. 5% ）. Conclusion The orthotopic transplanted model of gastric cancer with peritoneal carcinomatosis in nude mice was successfully established and reproduced the typical features of poorly differentiated adenocarcinoma.

关 键 词：胃癌 腹膜转移 原位移植 模型 动物 

分 类 号：R735.2[医药卫生—肿瘤]