Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest

Kobayashi,Kiyoyuki; Morishita,Asahiro; Iwama,Hisakazu; Fujita,Koji; Okura,Ryoichi; Fujihara,Shintaro; Yamashita,Takuma; Fujimori,Takayuki; Kato,Kiyohito; Kamada,Hideki; Niki,Toshiro; Hirashima,Mitsuomi; Okano,Keiichi; Suzuki,Yasuyuki; Masaki,Tsutomu

doi:10.3892/or.2015.4197

Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest

Authors:
- Kiyoyuki Kobayashi
- Asahiro Morishita
- Hisakazu Iwama
- Koji Fujita
- Ryoichi Okura
- Shintaro Fujihara
- Takuma Yamashita
- Takayuki Fujimori
- Kiyohito Kato
- Hideki Kamada
- Toshiro Niki
- Mitsuomi Hirashima
- Keiichi Okano
- Yasuyuki Suzuki
- Tsutomu Masaki
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Affiliations: Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan, Life Science Research Center, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan, Department of Immunology, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan, Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
Published online on: August 10, 2015 https://doi.org/10.3892/or.2015.4197
Pages: 1761-1770

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Abstract

Cholangiocarcinoma is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Galectin-9 (Gal-9) is a tandem-repeat-type galectin that has recently been shown to exert antiproliferative effects on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human cholangiocarcinoma cells in vitro as well as the microRNAs (miRNAs) associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of cholangiocarcinoma cell lines in vitro and the growth of human cholangiocarcinoma cell xenografts in nude mice. Our data further revealed that Gal-9 increased caspase‑cleaved keratin 18 (CCK18) levels, and the expression of cytochrome c increased in Gal-9-treated cholangiocarcinoma cell lines. These data suggested that Gal-9 induced cholangiocarcinoma cell apoptosis via the intrinsic apoptosis pathway mediated by caspase-dependent or -independent pathways. In addition, Gal-9 reduced the phosphorylation of the epidermal growth factor receptor (EGFR), insulin-like growth factor and insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor receptor and fibroblast growth factor receptor 3 (FGFR3). These findings suggest that Gal-9 can be a candidate of therapeutic target in the treatment of cholangiocarcinoma.

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