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Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer

Cancer Gene Therapy volume 23, pages 278–283 (2016)Cite this article

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Abstract

Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pancreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied. Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 24590977. Momotaro-Gene holds the patents for the REIC/DKK3 agent and develops the agent as a cancer therapeutic.

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Authors and Affiliations

  1. Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    H Sawahara, H Shiraha, D Uchida, H Kato, T Nagahara, M Iwamuro, J Kataoka, S Horiguchi, A Takaki, K Nouso & H Okada

  2. Departments of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    M Iwamuro

  3. Departments of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    M Watanabe & Y Nasu

  4. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan

    M Watanabe & Y Nasu

  5. Departments of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    M Sakaguchi

  6. Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    H Kumon

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  1. H Sawahara
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Corresponding author

Correspondence to H Shiraha.

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Competing interests

MW, MS, YN and HK own stocks in Momotaro-Gene. The remaining authors declare no conflict of interest.

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Sawahara, H., Shiraha, H., Uchida, D. et al. Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer. Cancer Gene Ther 23, 278–283 (2016). https://doi.org/10.1038/cgt.2016.31

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