Promising gene therapy using an adenovirus vector carrying reic/dkk-3 gene for the treatment of biliary cancer

Emi Tanaka, Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Atsushi Ohyama, Masaya Iwamuro, Masami Watanabe, Hiromi Kumon, Hiroyuki Okada


10 被引用数 (Scopus)


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.

ジャーナルCurrent Gene Therapy
出版ステータスPublished - 2020

ASJC Scopus subject areas

  • 分子医療
  • 分子生物学
  • 遺伝学
  • 創薬
  • 遺伝学(臨床)


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