Abstract
Background: We previously demonstrated that the reduced expression in immortalized cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis in pancreatic cancer and hepatocellular carcinoma. Objective: In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second-generation Ad-REIC (Ad-SGE-REIC). Methods: Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining. The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western blotting. Results: Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a mouse xenograft model. This effect was further enhanced in combination with cisplatin. Conclusion: Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells. REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.
Original language | English |
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Pages (from-to) | 64-70 |
Number of pages | 7 |
Journal | Current Gene Therapy |
Volume | 20 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- Apoptosis
- Biliary cancer
- Chemotherapy
- Cisplatin
- Gene therapy
- REIC/Dkk-3
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Drug Discovery
- Genetics(clinical)