Establishment and application of an orthotopic murine bladder cancer model

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. METHODS: 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. RESULTS: 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%, P0.05). CONCLUSION: 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.