荷瘤裸鼠膀胱癌原位模型的建立及VEGFsiRNA转染对肿瘤生长的影响

Construction of nude mouse model of bladder carcinoma in situ and effect of VEGFsiRNA transfection on tumor

目的:建立模拟人的荷瘤裸鼠膀胱癌原位模型,评价经VEGFsiRNA转染的人膀胱移行细胞癌T24细胞和未经转染的T24细胞在裸鼠膀胱内的成瘤状况。方法:采用细胞移植法分别将转染和未转染的T24细胞移植到裸鼠膀胱内后用核磁共振成像(MRI)定期检测,并在28d时处死动物称瘤重量,测定瘤体积,进行组织病理学和细胞学检查。结果:两组裸鼠膀胱内的总成瘤率为90%(36/40),转染组瘤细胞生长速度明显缓于未转染组。转染组和未转染组的重量和体积分别为:(1.1±0.3)g,(1.6±0.5)g;(805±172)mm3和(1389±294)mm3,两组比较差异具有显著性(P<0.05)。组织病理学和细胞学检查结果表明,转染组T24细胞恶性程度降低,浸润转移能力减弱,未转染组T24细胞恶性程度未发生改变,表现出极强的浸润转移倾向。结论:模拟人的荷瘤裸鼠膀胱癌原位模型更接近人体膀胱肿瘤的向膀胱腔内生长过程,荷瘤裸鼠膀胱癌原位模型可用于研究开发新型膀胱内抗肿瘤生物免疫制剂和抗癌化疗药物临床前期评价。

Objeotive To establish the nude mouse model of human bladder carcinoma in situ and observe the formation course of human bladder transitional cell carcinoma in mouse bladders, which induced by VEGFsiRNA- transfected T24 cells or untransfected T24 cells. Methods The nude mice were transplanted with VEGFsiRNA- transfected T24 cells or untransfected T24 cells into their bladders. The imageologic alterations were observed periodicly with MRI examination and the mice were sacrificed 48 d later. The weight and the volume of the tumor were tested, and the histopathologic and cytologic test were performed at the same time. Results The total ratio of the tumor formation as 90 percent （36/40） and the tumor growth speed in transfected group was much slower than that in untransfected group. The tumor weights in transfected group and untransfected group were （1.1±0.3） g and （1.6±0. 5） g, respectively, and the volumes of the tumor in transfected and untransfected groups were （805± 172） mm^3 and （1389±294） mm^3. The differences of tumor weight and volume between two groups were both significant （P〈0.05）. While the cell grade and malignant degree in untransfected group were higher than those in transfected group. Conclusion The nude mouse model of human bladder carcinoma in situ can simulate the character of intra-bladder lacuna-growing of human bladder carcinoma in situ. The nude mouse model of human bladder carcinoma in situ has great importance in the research and exploration of new intro-bladder antineoplastic biological agent. It is an important way to value the effectiveness of chemical anticaneer drugs preclinically.