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Updated: Mar 26, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Guizhi Fuling Wan as a Novel Agent for Intravesical Treatment for Bladder Cancer in a Mouse Model
Chi-Chen Lu1,2,3, Cheng-Huang Shen4,5, Chia-Bin Chang2,3
1Department of Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
Abstract:
Alternative intravesical agents are required to overcome the side effects currently associated with the treatment of bladder cancer. This study used an orthotopic bladder cancer mouse model to evaluate Guizhi Fuling Wan (GFW) as an intravesical agent. The effects of GFW were compared with those of mitomycin-C (Mito-C) and bacille Calmette-Guérin (BCG). We began by evaluating the response of the mouse bladder cancer cell line MB49 to GFW treatment, with regard to cell viability, cell cycle progression and apoptosis. MB49 cells were subsequently implanted into the urothelial walls of the bladder in female C57BL/6 mice. The success of the model was confirmed by the appearance of hematuria and tumor growth in the bladder. Intravesical chemotherapy was administered in accordance with a published protocol. In vitro data revealed that GFW arrested MB49 cell cycle in the G0/G1 phase, resulting in the suppression of cell proliferation and induced apoptosis. One possible mechanism underlying these effects is an increase in intracellular reactive oxygen species (ROS) levels leading to the activation of ataxia telangiectasia-mutated (ATM)/checkpoint kinase 2 (CHK2) and ATM/P53 pathways, thereby mediating cell cycle progression and apoptosis, respectively. This mouse model demonstrates the effectiveness of GFW in the tumor growth, with results comparable to those achieved by using BCG and Mito-C. Furthermore, GFW was shown to cause only mild hematuria. The low toxicity of the compound was confirmed by a complete lack of lesions on bladder tissue, even after 10 consecutive treatments using high concentrations of GFW. These results demonstrate the potential of GFW for the intravesical therapy of bladder cancer.
Insights
Guizhi Fuling Wan (GFW) shows promise as an intravesical agent for bladder cancer, effectively inhibiting tumor growth and inducing apoptosis with low toxicity. Its efficacy in a mouse model suggests potential as an alternative to current treatments like mitomycin-C and bacille Calmette-Guérin.
Area of Science:
- Oncology
- Pharmacology
- Urology
Background:
- Current intravesical treatments for bladder cancer present significant side effects.
- There is a need for alternative intravesical agents with improved safety profiles.
Purpose of the Study:
- To evaluate Guizhi Fuling Wan (GFW) as an intravesical agent for bladder cancer treatment.
- To compare the efficacy and toxicity of GFW with mitomycin-C (Mito-C) and bacille Calmette-Guérin (BCG).
Main Methods:
- An orthotopic bladder cancer mouse model using MB49 cells and female C57BL/6 mice was established.
- In vitro studies assessed GFW's effects on MB49 cell viability, cell cycle, and apoptosis.
- Intravesical chemotherapy with GFW, Mito-C, and BCG was administered, and tumor growth and bladder tissue were analyzed.
Main Results:
- GFW inhibited MB49 cell proliferation by arresting the cell cycle in the G0/G1 phase and induced apoptosis.
- GFW treatment led to a significant reduction in tumor growth, comparable to BCG and Mito-C.
- GFW demonstrated low toxicity, causing only mild hematuria and no bladder tissue lesions even at high concentrations.
Conclusions:
- GFW is effective in suppressing bladder cancer tumor growth and inducing apoptosis.
- GFW exhibits a favorable safety profile with minimal side effects compared to conventional agents.
- GFW holds potential as a novel intravesical therapy for bladder cancer.
