人胰腺癌细胞株PANC1裸鼠原位模型的建立及磁共振监测

Establishment and magnetic resonance imaging monitoring of the orthotopic transplantation nude mouse model with human pancreatic cancer cell line PANC1

目的建立一种稳定的人胰腺癌裸小鼠原位移植瘤模型，并探讨无创的磁共振（MRI）对其监测的应用价值。方法人胰腺癌细胞株PANC1体外常规传代后建立裸鼠皮下种植瘤模型，将皮下种植瘤制成细胞悬液，植入20只BALB／C．nu裸鼠的胰腺包膜下构建人胰腺癌原位移植模型；通过MRI检查监测模型的成瘤率、成瘤时间、肿瘤生长速度、肿瘤形态、信号变化等特征，于第7周末取肿瘤组织行病理学检查。结果接种后15d，7只（35％）荷瘤鼠在MRI上显示成瘤，至接种后27d，成瘤率为100％。肿瘤信号与邻近组织相比，90％（18／20）病灶T2WI呈均匀稍低信号，10％（2／20）呈等信号；75％（15／20）在T2WI呈均匀高信号。移植后2、3、4、5、6、7周经MRI测量的移植瘤体积分别为（12．6±2．4）mm^3、（94．3±11．2）mm^3、（175．9±82．5）mm^3、（395．8±126．6）mm^3、（1290．2±167．2）mm^3、（1583．4±87．4）mm^3。病理学检查确诊为胰腺低分化腺癌，并保持原发瘤的生物学特征。结论人胰腺癌细胞株PANC1移植瘤制成的细胞悬液种植裸小鼠胰腺包膜下制备胰腺癌模型符合人胰腺癌的特征，且易于无创监测，为临床研究提供了一个有效、稳定的体内实验体系。

Objective To establish a stable orthotopic transplantation nude mouse model of the human pancreatic cancer and to explore the role of monitoring tumor growth with noninvasive MRI. Methods The tumors cells suspension made by the subcutaneous injection of human pancreatic cancer cell lines PANC1 were used as the source of tissue for orthotopie implantation of tissue, and transplanted into the pancreas of 20 BALB/C- nu nude mice. After implantation, the successful rate, tumor formation time, tumor growth speed, tumor shape and the change of signal of the tumor were monitored and recorded noninvasively by MRI. At the end of the 7th week, all the specimens were examined by pathological methods. Results Thirty-five percent （7/20） mice with implantation of primary human PANC1 adenocareinoma cells were detected to have orthotopic implanted tumors by MRI after 15 days, and all the 20 nude mice developed pancreatic tumor within 27 days after operations, and the successful rate was 100%. Compared with adjacent normal tissue, the T1WI imaging of 90% （ 18/20 ） of all the tumors showed uniformly hypo-intense signal, 10% （ 2/20 ） showed iso-intense signal, the T/W 75% （15/20） showed uniformly hyper-intense signal. The tumor size 2, 31 4, 5,6, 7 weeks after implantation was （12.6±2.4）mm^3、（94.3±11.2）mm^3、（175.9±82.5）mm^3、（395.8±126.6）mm^3、（1290.2±167.2）mm^3、（1583.4±87.4）mm^3 , respectively. Pathologic examination confirmed poorly differentiated pancreatic adenoearcinoma and it remained the primary tumor＇s biologic features. Conclusions The orthotopic transplantation nude mouse model was in accordance with the feature of human pancreatic cancer and was easy for noninvasive monitoring, which provided an effective and stable in vivo experimental system.