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Published on: April 27, 2018
Gene therapy approach in prostate cancer cells using an active Wnt signal
Nis Giladi1, Hadas Dvory-Sobol, Eyal Sagiv
1The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel.
Background:
Functional activation of beta-catenin/T-cell factor (Tcf) signaling plays an important role in the early events of carcinogenesis. In past recent years accumulated evidence has demonstrated a significant role for the Wnt pathway in the development and progression of human prostate cancer. The objective of the current study was to use a gene-targeting approach to selectively kill human prostate cancer cells with activated beta-catenin/Tcf signaling.
Methods:
A recombinant adenovirus that carries a lethal gene (PUMA) under the control of a beta-catenin/T-cell factor (Tcf)-responsive promoter (Ad-TOP-PUMA), was used to selectively target human prostate cancer cells (PC-3) in which the beta-catenin/Tcf pathway is activated, and compared its killing efficiency in cancer cells in which this pathway is inactive (DU145 cells). Ad-FOP-PUMA, carrying a mutant Tcf binding site, was used as a control virus. Cell viability was measured by methylene blue assay, and the level of beta-catenin/Tcf activity was measured by luciferase assay.
Results:
The Ad-TOP-PUMA adenovirus inhibited PC-3 cell growth in a dose and time-dependent fashion, but did not had any effect on DU145 cell growth.
Conclusions:
Selective targeting of prostate cancer cells with the activated beta-catenin pathway may be a novel and effective therapy in prostate cancer.
Insights
A novel gene-targeting therapy using Ad-TOP-PUMA adenovirus selectively killed prostate cancer cells with activated beta-catenin/T-cell factor (Tcf) signaling. This approach shows promise for treating prostate cancer by targeting specific molecular pathways.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Beta-catenin/T-cell factor (Tcf) signaling is crucial in early carcinogenesis.
- The Wnt pathway significantly contributes to prostate cancer development and progression.
Purpose of the Study:
- To develop a gene-targeting strategy to selectively eliminate human prostate cancer cells exhibiting activated beta-catenin/Tcf signaling.
Main Methods:
- Utilized a recombinant adenovirus (Ad-TOP-PUMA) with a PUMA lethal gene under a Tcf-responsive promoter.
- Tested Ad-TOP-PUMA on prostate cancer cells (PC-3) with activated signaling versus inactive signaling (DU145).
- Assessed cell viability via methylene blue assay and Tcf activity via luciferase assay.
Main Results:
- Ad-TOP-PUMA demonstrated dose- and time-dependent inhibition of PC-3 cell growth.
- No significant effect on DU145 cell growth was observed, indicating pathway-specific targeting.
Conclusions:
- Selective targeting of prostate cancer cells with activated beta-catenin pathways represents a potential novel therapeutic strategy.
- This gene-targeting approach offers a promising avenue for prostate cancer treatment.
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