Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo

Fujita,Koji; Iwama,Hisakazu; Sakamoto,Teppei; Okura,Ryoichi; Kobayashi,Kiyoyuki; Takano,Jitsuko; Katsura,Akiko; Tatsuta,Miwa; Maeda,Emiko; Mimura,Shima; Nomura,Takako; Tani,Joji; Miyoshi,Hisaaki; Morishita,Asahiro; Yoneyama,Hirohito; Yamana,Yuka; Himoto,Takashi; Okano,Keiichi; Suzuki,Yasuyuki; Niki,Toshiro; Hirashima,Mitsuomi; Masaki,Tsutomu

doi:10.3892/ijo.2015.2941

Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo

Authors:
- Koji Fujita
- Hisakazu Iwama
- Teppei Sakamoto
- Ryoichi Okura
- Kiyoyuki Kobayashi
- Jitsuko Takano
- Akiko Katsura
- Miwa Tatsuta
- Emiko Maeda
- Shima Mimura
- Takako Nomura
- Joji Tani
- Hisaaki Miyoshi
- Asahiro Morishita
- Hirohito Yoneyama
- Yuka Yamana
- Takashi Himoto
- Keiichi Okano
- Yasuyuki Suzuki
- Toshiro Niki
- Mitsuomi Hirashima
- Tsutomu Masaki
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Affiliations: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan, Life Science Research Center, Kagawa University, Kagawa 761-079, Japan, Department of Gastroenterological Surgery, Kagawa University, Kagawa 761-079, Japan, Department of Immunology and Immunopathology, Kagawa University, Kagawa 761-079, Japan
Published online on: March 30, 2015 https://doi.org/10.3892/ijo.2015.2941
Pages: 2419-2430

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Abstract

Galectin-9, a soluble β-galactoside-binding animal lectin, evokes apoptosis in various human cancer cell lines. The galectin-9 antitumor effect against hepatocellular carcinoma (HCC) is, however, unknown. We investigated whether galectin-9 suppresses HCC growth in vitro and in vivo. We assessed the antitumor effect of galectin-9 on HCC cells by conducting WST-8 assay in vitro and xenograft model analysis in vivo. Galectin-9-induced apoptosis was evaluated by FACS and ELISA in vitro and by TUNEL stain in vivo. Cell cycle alteration was profiled by FACS. Caspases were profiled by colorimetry. MicroRNAs related to the galectin-9 antitumor effects were determined using microarrays, and their antitumor effect was confirmed in a transfection study in vitro. The expression levels of the target proteins of the miRNAs extracted above were analyzed by western blot analysis. To summarize the results, galectin-9 inhibited the growth of the HCC cell lines HLE and Li-7 in vitro and Li-7 in vivo inducing apoptosis. Cell cycle turnover was not arrested in HLE and Li-7 cells in vitro. miR‑1246 was similarly extracted both in vitro and in vivo, which sensitized Li-7 cells to apoptosis when transfected into the cells. DYRK1A, a target protein of miR‑1246 was downregulated in Li-7 cells. Caspase-9 was upregulated in Li-7 cells in vitro and in vivo. In conclusion, galectin-9 inhibited the growth of HCC cells by apoptosis, but not cell cycle arrest, in vitro and in vivo. miR‑1246 mediated signals of galectin-9, possibly through miR‑1246-DYRK1A-caspase-9 axis. Galectin-9 might be a candidate agent for HCC chemotherapy.

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