裸鼠前列腺原位肿瘤模型的建立

Establishment of prostate cancer model by orthotopic injection of human prostate cancer cell line Du145

目的: 建立一种裸鼠前列腺癌原位模型. 方法: 在10只裸鼠下腹部切口,显露膀胱和前列腺,用1 mL TB针筒、29G针头在其前列腺左右腹侧叶包膜下接种人前列腺癌DU145细胞50 μL,共计6×106个,以建立原位肿瘤模型,观察裸小鼠生命体征变化. 于濒死状态下处死,并取原位肿瘤、膀胱、盆腔淋巴结、肺脏和肝脏标本,用40 g/L甲醛固定、石蜡包埋和HE染色后显微镜下观察,X线照射显示骨骼转移情况. 结果: 10只裸鼠中有6只模型建立成功. 接种后14 d左右,可触及前列腺部位有黄豆大小的包块,质硬. 19 d后出现恶液质,解剖后发现前列腺部位有包块生长,直径约在0.8～1.5 cm,其中2例侵及膀胱. 肝脏泛黄、被膜皱缩,镜下呈急性重型肝炎的病理改变. 结论: 小鼠前列腺原位移植瘤模型建立成功.

AIM： To establish a prostate cancer orthotopic injection model in nude mice and to discuss its value of application. METHODS： Lower abdominal incision was made in 10 male nude mice. After the bladder and prostate were exposed, Du145 （6 × 10^6） was injected in ventral prostate lobes under the prostatic capsule by a TB syringe with a 29- gauge needle at 50 μL per mouse. The abdominal wall and skin were then closed with 7-0 surgical suture and the vital signs of the nude mice were observed. When the mice were dying, they were sacrificed. After the mouse was killed, the tissues of prostate, bladder, lymphatic node, lung and liver were taken out, fixed in 40 g/L formaldehyde, embedded in paraffin, stained by HE and then observed microscopically. The bone metastasis was observed by X-ray. RESULTS.. The incidence of primary tumor after intraprostatic injection was 60% （6 of 10）. About 14 d later, there were small palpable nodes in prostate and about 19 d later, cachexia occurred in nude mice. After dissection, it was shown that the diameter of primary tumors varied from 0.8 cm to 1.5 cm and the envelope of the liver became crimpy. Acute hepatitis could be observed under microscopy, which represented a large scale of hepatocyte death, liver sinus dilatation and hyperemia, hepatic Iobule infiltrated by lymphocyte and macrophage and inconspicuous hyperplasia. CONCLUSION： The orthotopic injection model is an optimal animal model to study the occurrence and development of prostate cancer. It mimics the natural situation of human prostate cancer and will help to understand the mechanismsof androgen-independence and osseous metastasis andtumor-host determinants of prostate specific antigen （PSA）expression.