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Updated: May 21, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer
Takeshi Hirata1, Masami Watanabe, Haruki Kaku
1Department of Urology,Okayama University, Okayama, Japan.
Abstract:
Bladder cancer is one of the most common urogenital malignancies. The intravesical instillation of anticancer agents is an attractive strategy to treat a superficial lesion or floating/disseminated cancer cells after transurethral operation. An adenovirus carrying REIC/Dkk-3, a tumor suppressor gene (Ad-REIC), exhibits cancer-specific apoptotic effects in various types of cancer cells. The aim of the present study was to examine the potential of Ad-REIC as a therapeutic agent for bladder cancer. KK47 and RT4 human bladder cancer cells were sensitive to the Ad-REIC treatment for apoptosis induction, but some human bladder cancer cell lines (T24, J82 and TccSup) were resistant. Significant cell growth inhibition was observed when these resistant cancer cell lines were treated with Ad-REIC in a condition of floating cells, which is clinically observed after transurethral operation and becomes a cause of intravesical cancer dissemination. The therapeutic potential of Ad-REIC for the treatment of multidrug-resistant bladder cancer was investigated. The adriamycin-resistant KK47 bladder cancer cells (KK47/ADM), which also present multidrug resistance, showed induction of significant apoptosis following Ad-REIC treatment. The Ad-REIC treatment induced downregulation of P-glycoprotein in KK47/ADM cells and restored the sensitivity to doxorubicin (adriamycin). Ad-REIC suppressed P-glycoprotein expression in a c-Jun-NH2-kinase (JNK)-dependent manner. Therefore, the current study indicated two therapeutic aspects of the Ad-REIC agent against human bladder cancer cells, as an apoptosis inducer/cell growth inhibitor and as a sensitizer of chemotherapeutic agents in multidrug-resistant cancer cells. The intravesical instillation of Ad-REIC could be an attractive therapeutic method in human bladder cancer where the treatment of superficial lesions and floating/disseminated or multidrug-resistant cancer cells is necessary.
Insights
Adenovirus carrying REIC/Dkk-3 (Ad-REIC) induces apoptosis in bladder cancer cells and inhibits growth of resistant cells. Ad-REIC also resensitizes multidrug-resistant bladder cancer to chemotherapy.
Area of Science:
- Oncology
- Gene Therapy
- Urology
Background:
- Bladder cancer is a common urogenital malignancy.
- Intravesical instillation of anticancer agents is a key treatment strategy.
- Floating cancer cells after surgery can cause dissemination.
Purpose of the Study:
- To evaluate Ad-REIC as a therapeutic agent for bladder cancer.
- To investigate Ad-REIC's efficacy against multidrug-resistant bladder cancer.
- To explore Ad-REIC's role in sensitizing resistant cells to chemotherapy.
Main Methods:
- Treatment of human bladder cancer cell lines (KK47, RT4, T24, J82, TccSup) with Ad-REIC.
- Assessment of apoptosis induction and cell growth inhibition.
- Investigation of Ad-REIC's effect on adriamycin-resistant KK47/ADM cells and P-glycoprotein expression.
Main Results:
- Ad-REIC induced apoptosis in sensitive bladder cancer cells (KK47, RT4).
- Ad-REIC inhibited growth of resistant cell lines (T24, J82, TccSup) as floating cells.
- Ad-REIC induced apoptosis in multidrug-resistant KK47/ADM cells, downregulating P-glycoprotein and restoring doxorubicin sensitivity via JNK pathway.
Conclusions:
- Ad-REIC demonstrates dual therapeutic potential: inducing apoptosis/inhibiting growth and sensitizing multidrug-resistant bladder cancer.
- Intravesical Ad-REIC instillation is a promising strategy for superficial, disseminated, or multidrug-resistant bladder cancer.
