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Updated: Aug 10, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
The effect of antisense Bcl-2 oligonucleotides on Bcl-2 protein expression and apoptosis in human bladder
B J Duggan1, P Maxwell, J D Kelly
1Uro-Oncology Research Group, Cancer Research Centre, Queen's University Belfast, Belfast, Northern Ireland, UK.
Purpose:
Bcl-2 is an important determinant of transitional cell carcinoma of the bladder recurrence and progression as well as a factor in patient response to chemotherapy or radiotherapy. We determined Bcl-2 down-regulation after antisense oligonucleotide therapy and synergism with mitomycin C in transitional cell carcinoma of the bladder.
Materials And Methods:
Bcl-2 protein was quantified using flow cytometry and immunohistochemistry in 4 bladder cancer cell lines, in bladder washings from 6 patients with carcinoma in situ and in 16 patient tumor samples. The synergistic effects of antisense oligonucleotides G3139 and 2009, and mitomycin C were investigated in 4 cell lines, while 2009 down-regulation was examined in 20 tumor explants in an ex vivo model.
Results:
Bcl-2 protein expression was found in all 4 cell lines and in 5 of the 6 cell populations derived from patients with carcinoma in situ. Of the 16 tumors 7 were classified positive by frozen section immunohistochemistry and quantitative flow cytometry. G3139 and 2009 down-regulated Bcl-2 protein expression in all 4 cell lines and 2009 down-regulated Bcl-2 protein expression in half of the Bcl-2 positive tumor specimens. There was only evidence in 1 cell line, T24/83, that Bcl-2 protein expression down-regulation enhanced mitomycin C induced apoptotic cell death.
Conclusions:
Bcl-2 was expressed in a significant proportion of bladder tumors and in carcinoma in situ. Therefore, antisense oligonucleotides represent a viable strategy for Bcl-2 protein down-regulation. However, it may not always translate into an increased level of mitomycin C induced apoptosis in transitional cell carcinoma of the bladder.
Insights
Antisense oligonucleotides can down-regulate Bcl-2 protein in bladder cancer. However, this may not consistently increase apoptosis when combined with mitomycin C in transitional cell carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bcl-2 protein is crucial in bladder cancer progression and treatment response.
- Understanding Bcl-2's role is key for developing targeted therapies.
Purpose of the Study:
- To investigate Bcl-2 down-regulation using antisense oligonucleotides.
- To assess the synergistic effects of antisense oligonucleotides and mitomycin C in bladder cancer.
Main Methods:
- Quantified Bcl-2 protein via flow cytometry and immunohistochemistry.
- Tested antisense oligonucleotides (G3139, 2009) and mitomycin C in cell lines and ex vivo tumor models.
Main Results:
- Bcl-2 expression confirmed in bladder cancer cell lines, carcinoma in situ, and tumors.
- Antisense oligonucleotides successfully down-regulated Bcl-2 protein.
- Enhanced mitomycin C-induced apoptosis was observed in only one cell line.
Conclusions:
- Antisense oligonucleotides are a viable strategy for Bcl-2 down-regulation in bladder cancer.
- The therapeutic benefit of combining these agents may vary, requiring further investigation.
