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Promising Gene Therapy Using an Adenovirus Vector Carrying REIC/Dkk-3 Gene for the Treatment of Biliary Cancer

Author(s):

Emi Tanaka, Daisuke Uchida*, Hidenori Shiraha, Hironari Kato, Atsushi Oyama, Masaya Iwamuro, Masami Watanabe, Hiromi Kumon and Hiroyuki Okada   Pages 1 - 7 ( 7 )

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.

Conclusions: 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.

Keywords:

REIC/Dkk-3, gene therapy, apoptosis, biliary cancer, chemotherapy, cisplatin

Affiliation:

Okayama University, Department of Gastroenterology, Okayama University, Department of Gastroenterology, Okayama University, Department of Gastroenterology, Okayama University, Department of Gastroenterology, Okayama University, Department of Gastroenterology, Okayama University, Department of Gastroenterology, Okayama University Hospital, Center for Innovative Clinical Medicine, Okayama University, Innovation center Okayama for nanobio-targeted therapy, Okayama University, Department of Gastroenterology



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