Title:Promising Gene Therapy Using an Adenovirus Vector Carrying REIC/Dkk-3 Gene for the Treatment of Biliary Cancer
Volume: 20
Issue: 1
Author(s): Emi Tanaka, Daisuke Uchida*, Hidenori Shiraha, Hironari Kato, Atsushi Ohyama, Masaya Iwamuro, Masami Watanabe, Hiromi Kumon and Hiroyuki Okada
Affiliation:
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558,Japan
Keywords:
REIC/Dkk-3, gene therapy, apoptosis, biliary cancer, chemotherapy, cisplatin.
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.
