Related Experiment Video
Updated: Aug 24, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Systematic in vitro evaluation of survivin directed antisense oligodeoxynucleotides in bladder cancer cells
Susanne Fuessel1, Bernd Kueppers, Shuangli Ning
1Department of Urology and Institute of Pathology, Technical University Dresden, Dresden, Germany. susanne.fuessel@mailbox.tu-dresden.de
Purpose:
The rather poor responses to conventional treatment for bladder cancer (BCa) require novel, specific therapy approaches. The down-regulation of BCa associated genes may represent a new option to inhibit specifically BCa cell growth and induce cell death. Survivin, an apoptosis inhibitor that is up-regulated in the majority of malignancies, including BCa, provides an attractive target for molecular therapies, such as treatment with specific antisense oligode-oxynucleotides (AS-ODNs).
Materials And Methods:
We used mRNA secondary structure prediction to design survivin directed AS-ODNs. After lipid mediated transfection with 30 selected antisurvivin AS-ODN inhibitory effects on cell growth properties as well as on survivin expression were measured.
Results:
Three of 30 tested constructs reproducibly impaired the growth characteristics of 4 BCa cell lines. Detailed analysis of the cell line EJ28 treated with the constructs SVV261, SVV264 and SVV286 revealed a clear decrease in viability (down to 35%) and long-term proliferation (down to 14%), which were caused by cell cycle arrest and an increase in apoptosis (from 19.5% to 51.3% maximum). The inhibition of tumor cell growth was associated with up to 60% to 80% survivin expression down-regulation. Interestingly all 3 evolved AS-ODNs were directed against the putative single strand survivin mRNA motif between 274 to 285 nucleotides, identified by secondary structure prediction. The reported accessibility of this motif to other nucleic acid based inhibitors such as ribozymes and small interfering RNAs emphasizes the rationale of a systematic selection of mRNA target sites.
Conclusions:
The survivin directed AS-ODNs shown to inhibit effectively the proliferation of BCa cells in the current study may provide suitable adjuvant therapeutic agents for the specific local treatment of BCa.
Insights
Novel antisense oligodeoxynucleotides (AS-ODNs) targeting survivin effectively inhibit bladder cancer cell growth and proliferation. These survivin-directed AS-ODNs show promise as targeted therapeutic agents for bladder cancer treatment.
Area of Science:
- Molecular biology
- Oncology
- Biochemistry
Background:
- Conventional bladder cancer treatments show limited efficacy, necessitating novel therapeutic strategies.
- Targeting cancer-associated genes, such as the apoptosis inhibitor Survivin, offers a specific approach to inhibit cancer cell growth.
- Survivin is frequently overexpressed in bladder cancer, making it a prime target for molecular therapies.
Purpose of the Study:
- To design and evaluate survivin-directed antisense oligodeoxynucleotides (AS-ODNs) as a targeted therapy for bladder cancer.
- To assess the inhibitory effects of AS-ODNs on bladder cancer cell growth, proliferation, and Survivin expression.
Main Methods:
- mRNA secondary structure prediction was employed to design survivin-specific AS-ODNs.
- Lipid-mediated transfection was used to introduce 30 selected AS-ODNs into bladder cancer cell lines.
- Inhibitory effects on cell growth, viability, proliferation, cell cycle, apoptosis, and Survivin expression were quantified.
Main Results:
- Three out of 30 tested AS-ODNs (SVV261, SVV264, SVV286) significantly impaired bladder cancer cell growth.
- These AS-ODNs reduced cell viability to 35% and proliferation to 14% in EJ28 cells, inducing cell cycle arrest and increasing apoptosis.
- Survivin expression was downregulated by 60-80%, correlating with the observed inhibition of tumor cell growth.
- The effective AS-ODNs targeted a specific survivin mRNA motif identified by secondary structure prediction.
Conclusions:
- Survivin-directed AS-ODNs demonstrate potent inhibition of bladder cancer cell proliferation in vitro.
- These AS-ODNs represent potential adjuvant therapeutic agents for localized bladder cancer treatment.
- The study highlights the importance of targeting accessible mRNA motifs for effective nucleic acid-based therapies.
