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Updated: Aug 29, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Bladder cancer therapy using combined proliferating cell nuclear antigen antisense oligonucleotides and recombinant
Zhaohui Zhu1, Shian Xing, Chen Lin
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430022, China. zhuzhaohui316@hotmail.com
Objective:
To evaluate the antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and in vivo.
Methods:
Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6 micro mol/L) was then introduced into the cells using a cationic lipid (lipofectamine, 20 micro l/ml). In vitro and in vivo antitumor effects of combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry, clone formation, and a nude mice model.
Results:
The combination of PCNA-ASO and Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell lines. The ability of the cells to form foci was also reduced by 74.8% in EJ cells and by 67.5% in BIU-87 cells (P < 0.01). A significant decrease of cells in the S phase (11.4% in EJ cells, 14.6% in BIU-87 cells) and a significant increase of cells in G1 phase (62.2% in EJ, 56.8% in BIU-87) were noted. The mean tumor volume after 7 days of treatment with PCNA-ASO or Ad-p53 in combination decreased to 47.6% or 36.4% of the initial tumor size in the two cell lines respectively.
Conclusion:
These results indicate that combined PCNA-ASO and Ad-p53 in the treatment of bladder cancer with mutant p53 has important therapeutic potential, significantly suppressing the growth of human bladder cancer both in vitro and in vivo.
Insights
The combination of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) and recombinant adenovirus p53 (Ad-p53) shows significant potential for treating bladder cancer. This combined therapy effectively suppresses tumor growth in both laboratory and animal models.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Bladder cancer often involves mutations in the p53 tumor suppressor gene.
- Developing effective therapeutic strategies for bladder cancer remains a critical challenge.
Purpose of the Study:
- To evaluate the combined antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) and recombinant adenovirus p53 (Ad-p53).
- To assess the therapeutic potential of this combination against bladder cancer cell lines in vitro and in vivo.
Main Methods:
- Cells were treated with Ad-p53 and PCNA-ASO using cationic lipid transfection.
- Antitumor effects were assessed using MTT assays, flow cytometry, clone formation assays, and a nude mouse model.
Main Results:
- The combination significantly inhibited cell viability in EJ (89.3%) and BIU-87 (78.6%) bladder cancer cells.
- Colony formation was reduced, and cell cycle analysis showed a decrease in S phase and an increase in G1 phase.
- In vivo studies demonstrated a significant reduction in tumor volume with the combined treatment.
Conclusions:
- Combined PCNA-ASO and Ad-p53 therapy demonstrates significant therapeutic potential for bladder cancer, particularly in cases with mutant p53.
- This combination effectively suppresses human bladder cancer growth both in vitro and in vivo.
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