MKN-45人胃癌原位移植模型的建立及紫杉醇在该模型中的疗效评价  

Establishment of orthotopic transplantation model of MKN-45 human gastric cancer and evaluation of the efficacy of paclitaxel in this model

作　　者：钱可扬 蔡娟 岳武恒 丁寅[3] 钱汉清 刘宝瑞[1,4] Qian Keyang;Cai Juan;Yue Wuheng;Ding Ying;Qian Hanqing;Liu Baorui(The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China;The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China;School of Chemistry and Chemical Engineering, Nanjing University, State Key Laboratory of Bioanalytical Chemistry, Nanjing University, Nanjing 210023, China;The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China)

机构地区：[1]南京医科大学鼓楼临床医学院肿瘤中心,210008 [2]南京中医药大学中西医结合鼓楼临床医学院肿瘤中心,210008 [3]南京大学化学化工学院南京大学生命分析化学国家重点实验室,210023 [4]南京大学医学院附属鼓楼医院肿瘤中心,210008

出　　处：《中华实验外科杂志》2019年第3期427-431,共5页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金青年项目(81602106);江苏省自然科学基金青年项目(BK20150103);国家重点研发计划专项经费项目(2017YFC1308900).

摘　　要：目的建立可实时监测的人胃癌原位移植瘤模型,并利用活体成像系统可视化评价紫杉醇在该模型中的疗效。方法按照皮下成瘤-传代-原位移植的模式,采用原位移植技术将组织学完整的、稳定表达荧光素酶的人胃癌细胞MKN-45-luc移植至BALB/c(nu/nu)裸鼠胃壁浆膜下,术后第7、14天对小鼠进行活体成像,评价肿瘤原位移植模型的建立。成模裸鼠尾静脉注射紫杉醇(10 mg/kg)1次,活体成像观察小鼠肿瘤生长,记录小鼠体重变化与生存曲线。26 d后对小鼠移植瘤及转移瘤取材,苏木精-伊红(HE)染色观察肿瘤形态学特征,侵袭范围及转移情况。结果MKN-45-luc的细胞形态及对紫杉醇的敏感性与MKN-45差异无统计意义(P>0.05)。成功建立人胃癌原位移植模型,成瘤率为90%(18/20),小鼠出现淋巴结转移和肝脏转移,病理HE切片符合胃癌组织学特征。与对照组比较,成模小鼠紫杉醇给药后抑瘤效果明显。结论胃囊-OB胶法简便、高效,建立的胃癌原位移植模型与人胃癌生物学特征更相似。Objective To establish an orthotopic transplantation model of bioluminescent human gastric carcinoma and visually evaluate the therapeutic effect of paclitaxel in this model using in vivo imaging system. Methods The intact MKN-45-luc tumor tissue, stably expressing luciferase, was implanted into the gastric serosa of nude mice by orthotopic transplantation technique according to the subcutaneously implant-passage-orthotopic transplantation mode. Each mouse was photographed by in vivo fluorescence imaging system at the 7th and 14th day after surgery to evaluate the tumorigenecity. Paclitaxel was administered intravenously on tumor-bearing mice at the dose of 10 mg/kg. The changes of fluorescence intensity and weight were observed every 4 days. The fluorescence-positive mice were sacrificed after 26 days, and hematoxylin and eosin (HE) staining was performed to observe the morphology of endogastric xenograft tumor and metastasis. Results The morphology and paclitaxel sensitivity of MKN-45-luc were consistent with MKN-45 (P>0.05). The orthotopic model was successfully established, giving the successful rate of 90%(18/20), and lymph node metastasis and liver metastasis were observed. The histological characteristics of the tumor tissues from the model after HE staining were the same as gastric cancer. Compared with the control group, paclitaxel had a significant anti-tumor effect after administration on this mice model. Conclusion It is convenient and efficient to establish the orthotopic transplantation model of gastric cancer using gastric bursa-OB glue method.

关 键 词：胃癌 原位移植模型 胃囊-OB胶法 紫杉醇 活体生物成像 

分 类 号：R735.2[医药卫生—肿瘤]