Yang Shen-Min, Wen Duan-Gai, Hou Jian-Quan, He Jun, Cen Jian-Nong, Chen Jian-Hua
Department of Urology, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, 215006, PR China.
Ai Zheng. 2007 Apr;26(4):341-5.
BACKGROUND & OBJECTIVE: The recurrence rate of superficial bladder cancer is still high even the patients received postoperative intravesical infusion of chemotherapeutic drugs, such as mitomycin C (MMC). Some studies showed that intravesical infusion of small interfering RNA (siRNA) could suppress the growth of bladder cancer in nude mice. This study was to establish an orthotopic animal model bearing human bladder cancer, monitor tumor progression by magnetic resonance imaging (MRI), and observe the synergistic effect of survivin short hairpin RNA (shRNA) in combination with MMC for intravesical treatment using this animal model.
Human bladder cancer cell line T24 was inoculated into the bladders of 25 BALB/c nude mice to establish orthotopic bladder cancer model. MRI was performed to monitor tumor progression, using Gd-DTPA as contrast agent. The pathologic morphology of the bladders was observed. Eighteen mice bearing bladder cancer were randomized into 3 groups: untreated group, MMC group, and combination group. The bladders were weighed after 6 intravesical infusions.
All the 25 mice developed bladder cancer after T24 cell inoculation. On MRI, no change in the bladders was observed at 7 days after inoculation, filling defect in the bladders, accordant to actual tumor size, was detected at 14, 21, and 28 days after inoculation. Pathologic examination showed that tumors grew in mucosa of the bladders at 7 days after inoculation, infiltrated into muscle layer at 14-28 days after inoculation, and invaded serosa at 35 days after inoculation. The inhibition rate of tumor growth was significantly higher in combination group than in MMC group (56.34% vs. 33.45%, P<0.05).
We successfully established an orthotopic bladder cancer model, which could simulate the progression of human bladder cancer approximately. MRI is a reliable way for dynamic detection of murine orthotopic bladder tumor. Down-regulating survivin expression by RNA interference could enhance the antitumor effect of MMC.
即使浅表性膀胱癌患者接受了术后膀胱内灌注化疗药物，如丝裂霉素C（MMC），其复发率仍然很高。一些研究表明，膀胱内灌注小干扰RNA（siRNA）可抑制裸鼠膀胱癌的生长。本研究旨在建立人膀胱癌原位动物模型，通过磁共振成像（MRI）监测肿瘤进展，并观察生存素短发夹RNA（shRNA）与MMC联合膀胱内治疗在该动物模型中的协同作用。
将人膀胱癌细胞系T24接种于25只BALB/c裸鼠膀胱内，建立原位膀胱癌模型。以钆喷酸葡胺（Gd-DTPA）为对比剂，行MRI监测肿瘤进展。观察膀胱的病理形态。18只荷膀胱癌小鼠随机分为3组：未治疗组、MMC组和联合组。膀胱内灌注6次后称量膀胱重量。
接种T24细胞后，25只小鼠均发生膀胱癌。MRI检查显示，接种后7天膀胱无变化，接种后14、21和28天膀胱出现充盈缺损，与实际肿瘤大小相符。病理检查显示，接种后7天肿瘤生长于膀胱黏膜，接种后14 - 28天浸润至肌层，接种后35天侵犯浆膜。联合组肿瘤生长抑制率显著高于MMC组（56.34%对33.45%，P<0.05）。
我们成功建立了原位膀胱癌模型，该模型可大致模拟人膀胱癌的进展。MRI是动态检测小鼠原位膀胱肿瘤的可靠方法。通过RNA干扰下调生存素表达可增强MMC的抗肿瘤作用。
