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Updated: Jun 14, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
A rat model of intravesical delivery of small interfering RNA for studying urinary carcinoma
Carl-Jørgen Arum1, Yosuke Kodama, Natale Rolim
1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Purpose:
siRNA has been used successfully in loss-of-function studies in vitro, but neither in vivo nor in clinical applications. The aims of the present study were (1) to establish rat models for in vivo delivery of siRNA to bladder cancer, and (2) to identify potential targets for siRNA.
Methods:
The rat models of human urinary carcinoma and rat urinary carcinoma cell line (AY-27) were induced by tobacco-related chemical carcinogens, either N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). A syngeneic orthotopic bladder cancer model was established by inoculation of AY-27 cells. A fluorescence-labelled negative control siRNA with cationic and neutral liposomes was tested both in vitro (AY-27 cells) and in vivo.
Results:
siRNA was highly accumulated in the cancer cells as early as 12 h and remained at least for 24 h after a single dose in vivo. Numerous CD3+ T cells appeared mainly in the periphery area of the tumour. Bioinformatics analysis revealed a list of concordantly highly expressed genes, possible siRNA targets, in the animal models as well as human urinary carcinoma. Literature search on siRNA and bladder cancer provided a list of genes used as siRNA targets.
Conclusion:
The methodology and data presented in the present study provide a number of opportunities for basic research on urinary carcinogenesis and for translational research on evaluation of siRNA therapeutic strategies for urinary carcinoma in the native organ, where hormonal, neural and immunological processes more closely resemble the clinical situation.
Insights
This study establishes rat models for in vivo delivery of small interfering RNA (siRNA) to bladder cancer, identifying potential therapeutic targets. The findings support siRNA
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Small interfering RNA (siRNA) has shown promise in vitro for loss-of-function studies.
- Challenges remain in its in vivo and clinical application for cancer therapy.
Purpose of the Study:
- To develop rat models for in vivo siRNA delivery to bladder cancer.
- To identify potential siRNA targets for bladder cancer treatment.
Main Methods:
- Rat models of human urinary carcinoma were induced using chemical carcinogens (FANFT or BBN).
- A syngeneic orthotopic bladder cancer model was created using AY-27 cells.
- Fluorescence-labeled siRNA with liposomes was tested in vitro and in vivo.
Main Results:
- siRNA demonstrated high accumulation in cancer cells within 12 hours, persisting for at least 24 hours post-administration.
- Significant infiltration of CD3+ T cells was observed around the tumor periphery.
- Bioinformatics and literature analysis identified potential siRNA target genes.
Conclusions:
- The developed models facilitate in vivo research on urinary carcinogenesis.
- The study provides a foundation for evaluating siRNA-based therapeutic strategies for bladder cancer in a more clinically relevant setting.
