人肺癌原位移植瘤模型的建立及活体成像观察

Establishment of Orthotopic Transplant Model of Human Lung Cancer and Observation of In vivo Biofluorescent Imaging in Nude Mice

目的 通过建立人肺癌原位移植瘤模型,研究人肺癌高、低转移细胞的体内生物学特性.方法 应用慢病毒转染的方法建立同时表达绿色荧光蛋白及荧光素酶（GFP/Luc）的人肺癌低转移细胞SPC-A-1和高转移细胞SPC-A-1sci,在此基础上,建立裸小鼠肺原位移植瘤动物模型,采用小动物活体成像技术和解剖学方法观察肿瘤在肺原位的生长及转移情况.结果 成功建立了稳定表达GFP/Luc的人肺癌高、低转移细胞,并成功建立了肺癌原位移植瘤动物模型.小动物活体成像系统检测显示,SPC-A-1-GFP-Luc和SPC-A-1 sci-GFP-Luc细胞模型中荧光素酶表达率分别为50％（12/24）和62.5％（20/32）,SPC-A-1 sci-GFP-Luc组荧光素酶表达的面积及表达强度高于SPC-A-1-GFP-Luc组.解剖学检查显示,SPC-A-1和SPC-A-lsci组的肺原位成瘤率分别为50％（12/24）和62.5％ （20/32）;体内自发转移率分别为25％ （3/12）和40％ （8/20）.结论 通过建立肺原位移植瘤动物模型能够再现肿瘤在肺内的生长及转移等生物学特性,小动物活体成像系统能够对其生物学特性进行客观评价.

Objective To establish orthotopic transplant models of human lung cancer and study the in vivo biological characteristics of human lung cancer with high and low metastatic potential cells in nude mice. Methods The low-metastatic human lung cancer cell line SPC-A-1 and high-metastatic human lung cancer cell line SPC-A- 1 sci were tranfected with green fluorescent protein/Luciferase （GFP/ Luc） gene by lentiviral vector, they were orthotopically transplanted into the lung of nude mice. The tumor growth and metastasis were observed by using in vivo biofluoreseent imaging system and ana- tomical methods. Results The human lung cancer cell lines with stable high-level GFP/Luc expression and orthotopic transplant animal models were successfully established. In vivo biofluorescent images showed that the luciferase expression rates of SPC-A-1-GFP-Luc and SPC-A-1 sci-GFP-Luc cells were 50.0% （12/24） and 62.5% （20/32）, respectively. The expression intensity and area of luciferase expres- sion in SPC-A-1 sci-GFP-Luc cells were higher than that in SPC-A-1-GFP-Luc cells. Anatomical exami- nation showed that tumor formation rates of SPC-A-1 cells and SPC-A-lsci cells were 50.0% （12/24） and 62.5% （20/32）, respectively. Meanwhile, the spontaneous metastasis rate was 25.0% （3/12） and 40.0% （8/20） in vivo. Conclusions Lung orthotopic transplant animal model could reproduce the biological characteristics of tumor growth and metastasis. In vivo biofluorescent imaging system was suitable for the objective evaluation of the biological characteristics.