1. Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma.
- Author
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Sawahara, Hiroaki, Shiraha, Hidenori, Uchida, Daisuke, Kato, Hironari, Kato, Ryo, Oyama, Atsushi, Nagahara, Teruya, Iwamuro, Masaya, Horiguchi, Shigeru, Tsutsumi, Koichiro, Mandai, Mari, Mimura, Tetsushige, Wada, Nozomu, Takeuchi, Yasuto, Kuwaki, Kenji, Onishi, Hideki, Nakamura, Shinichiro, Watanabe, Masami, Sakaguchi, Masakiyo, and Takaki, Akinobu
- Subjects
LIVER cancer ,TUMOR suppressor genes ,APOPTOSIS ,IMMUNOCOMPETENT cells ,IMMUNE response ,LABORATORY mice - Abstract
Background and Aim Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed. Methods Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice. Results REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6). Conclusions Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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