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Updated: Jul 18, 2026

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Suppression of gastric cancer cell growth by targeting the beta-catenin/T-cell factor pathway
Hadas Dvory-Sobol1, Eyal Sagiv, Eliezer Liberman
1Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel.
Background:
Functional activation of beta-catenin/T-cell factor (Tcf) signaling plays an important role in the early events of carcinogenesis. Recently, it was demonstrated that adenomatous polyposis coli or beta-catenin genes are mutated frequently in gastric cancer cells. The objective of the current study was to use a gene-targeting approach to kill human gastric cancer cells selectively with activated beta-catenin/Tcf signaling.
Methods:
A recombinant adenovirus that carries a lethal gene (p53 up-regulated modulator of apoptosis [PUMA]) under the control of a beta-catenin/Tcf-responsive promoter (AdTOP-PUMA) was used selectively to target gastric cancer cells (AGS) that posses an active beta-catenin/Tcf pathway. The combined effect of AdTOP-PUMA and several chemotherapeutic agents (5-florouracil, doxorubicin, paclitaxel) also was evaluated. Cell viability was measured by methylene blue assay, protein expression was measured by Western blot analysis, and cell cycle and apoptosis were evaluated by fluorescent-activated cell sorter analysis. RESULTS.: The TOP-PUMA adenovirus inhibited AGS cell growth in a dose- and time-dependent fashion. Growth inhibition was associated with the up-regulation of PUMA expression and the induction of apoptosis. Chemotherapy synergistically enhanced the killing effect of AdTOP-PUMA.
Conclusions:
Selective targeting of gastric cancer cells with the activated beta-catenin pathway may be a novel and effective therapy in gastric cancer. Combination of this gene-therapy approach with standard therapy may improve efficacy and reduce toxicity.
Insights
This study developed a gene-targeting therapy using AdTOP-PUMA to selectively kill gastric cancer cells with activated beta-catenin/Tcf signaling. Combining this with chemotherapy enhanced cancer cell killing, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Beta-catenin/T-cell factor (Tcf) signaling is crucial in early carcinogenesis.
- Mutations in adenomatous polyposis coli or beta-catenin genes are common in gastric cancer.
- Targeting activated beta-catenin/Tcf signaling offers a potential therapeutic avenue for gastric cancer.
Purpose of the Study:
- To selectively eliminate human gastric cancer cells exhibiting activated beta-catenin/Tcf signaling.
- To evaluate the efficacy of a gene-targeting approach using a recombinant adenovirus carrying a lethal gene (PUMA).
- To assess the synergistic effects of this gene therapy combined with standard chemotherapeutic agents.
Main Methods:
- Utilized a recombinant adenovirus (AdTOP-PUMA) with a PUMA gene under a beta-catenin/Tcf-responsive promoter.
- Targeted gastric cancer cells (AGS) with active beta-catenin/Tcf pathway.
- Assessed cell viability, protein expression, cell cycle, and apoptosis.
- Evaluated the combined effects of AdTOP-PUMA and chemotherapeutic agents (5-fluorouracil, doxorubicin, paclitaxel).
Main Results:
- AdTOP-PUMA demonstrated dose- and time-dependent inhibition of AGS cell growth.
- Inhibited growth correlated with increased PUMA expression and apoptosis.
- Chemotherapy synergistically augmented the cell-killing effect of AdTOP-PUMA.
Conclusions:
- Selective targeting of gastric cancer cells with activated beta-catenin pathways represents a novel and effective therapeutic strategy.
- Combining gene therapy with standard chemotherapy may enhance treatment efficacy and reduce toxicity.
- This approach holds promise for improving outcomes in gastric cancer treatment.
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