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Updated: Mar 14, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Fiber-modified adenovirus-mediated suicide gene therapy can efficiently eliminate bladder cancer cells in vitro and
De-Gui Wang1, Mei-Jun Zhao1, Yong-Qiang Liu1
1Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Abstract:
Adenovirus-mediated gene therapy is a promising strategy for bladder cancer treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in bladder cancer cells decreases the infection efficiency of the therapeutic adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is driven by a human UPII promoter. Then, we tested the bladder cancer specificity of the UPII promotor and the expression of the HSV-TK protein. Additionally, we observed a potent cytotoxic effects of RGDAd-UPII-TK and ganciclovir (GCV) on bladder cancer as demonstrated by reduced cell survival and morphology changes in vitro. Furthermore, we confirmed that RGDAd-UPII-TK in combination with a GCV injection could significantly reduce the established T24 tumor growth and increase apoptosis in vivo. Altogether, our results indicated that the recombinant adenovirus RGDAd-UPII-TK could target bladder cancer through valid gene therapy.
Insights
This study developed a modified adenovirus for bladder cancer gene therapy, improving infection efficiency and demonstrating potent tumor reduction in vitro and in vivo. The RGD-modified adenovirus effectively targets and treats bladder cancer.
Area of Science:
- Oncolytic virology
- Gene therapy for cancer
- Bladder cancer research
Background:
- Adenovirus-mediated gene therapy shows promise for bladder cancer.
- Reduced coxsackie and adenovirus receptor (CAR) expression in bladder cancer cells limits therapeutic adenovirus infection efficiency.
Purpose of the Study:
- To develop and evaluate an Arg-Gly-Asp (RGD)-modified adenovirus (RGDAd-UPII-TK) for enhanced bladder cancer gene therapy.
- To assess the specificity of the human UPII promoter and the expression of the HSV-TK suicide gene.
- To determine the in vitro and in vivo efficacy of RGDAd-UPII-TK combined with ganciclovir (GCV).
Main Methods:
- Construction of RGDAd-UPII-TK, an adenovirus encoding the HSV-TK suicide gene under the human UPII promoter.
- Testing of UPII promoter specificity and HSV-TK protein expression in bladder cancer cells.
- In vitro assessment of RGDAd-UPII-TK and GCV cytotoxicity on bladder cancer cell survival and morphology.
- In vivo evaluation of RGDAd-UPII-TK and GCV efficacy in reducing T24 tumor growth and inducing apoptosis.
Main Results:
- The RGD modification enhanced adenovirus targeting of bladder cancer cells.
- The human UPII promoter demonstrated specificity for bladder cancer.
- RGDAd-UPII-TK combined with GCV exhibited significant cytotoxic effects, reducing cell survival and altering morphology in vitro.
- In vivo studies showed substantial reduction in established T24 tumor growth and increased apoptosis with RGDAd-UPII-TK and GCV treatment.
Conclusions:
- The RGD-modified adenovirus, RGDAd-UPII-TK, represents a viable strategy for targeted bladder cancer gene therapy.
- This approach overcomes CAR downregulation challenges in bladder cancer.
- The combination therapy demonstrates potent anti-tumor activity, offering a promising new avenue for bladder cancer treatment.
