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Updated: Jul 15, 2026
An Orthotopic Model of Murine Bladder Cancer
Published on: February 6, 2011
[Establishment and application of an orthotopic murine bladder cancer model]
Shen-Min Yang1, Duan-Gai Wen, Jian-Quan Hou
1Department of Urology, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, 215006, PR China.
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%, P<0.05).
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.
Insights
Combining survivin short hairpin RNA (shRNA) with mitomycin C (MMC) intravesical treatment significantly enhances bladder cancer suppression. This study established a reliable orthotopic bladder cancer model for evaluating novel therapeutic strategies.
Area of Science:
- Oncology
- Biotechnology
- Medical Imaging
Background:
- Superficial bladder cancer recurrence remains high despite standard intravesical chemotherapy like mitomycin C (MMC).
- Previous research suggests intravesical small interfering RNA (siRNA) can inhibit bladder cancer growth in animal models.
Purpose of the Study:
- To establish a human bladder cancer orthotopic animal model for evaluating intravesical treatments.
- To monitor tumor progression using magnetic resonance imaging (MRI).
- To assess the synergistic effect of survivin short hairpin RNA (shRNA) combined with MMC.
Main Methods:
- An orthotopic bladder cancer model was created in BALB/c nude mice using the human T24 bladder cancer cell line.
- Tumor progression was monitored non-invasively using MRI with Gd-DTPA contrast.
- Mice were randomized into untreated, MMC-treated, and combination (MMC + survivin shRNA) groups for intravesical therapy.
Main Results:
- The orthotopic model successfully simulated human bladder cancer progression, detectable by MRI from 14 days post-inoculation.
- Pathologic examination confirmed tumor growth from mucosa to muscle layer invasion and serosa invasion over 35 days.
- The combination group demonstrated a significantly higher tumor growth inhibition rate (56.34%) compared to the MMC-only group (33.45%, P<0.05).
Conclusions:
- A reliable orthotopic bladder cancer model was established, suitable for dynamic tumor monitoring via MRI.
- Down-regulating survivin expression using RNA interference potentiates the anti-tumor efficacy of MMC.
- This combination therapy shows promise for enhancing intravesical treatment of bladder cancer.
