title: Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo.
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.
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Life Science Research Center, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Iwama
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Okura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Jitsuko
authors.initials: J
authors.lastname: Takano
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Katsura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Tatsuta
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Maeda
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Shima
authors.initials: S
authors.lastname: Mimura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Tani
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Asahiro
authors.initials: A
authors.lastname: Morishita
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yoneyama
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamana
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Himoto
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Okano
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-079, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053453:Caspase 9 / Q000235:genetics; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000097603:Dyrk Kinases
chemical_list: D053453:Caspase 9; D037161:Galectins; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C105032:LGALS9 protein, human; C577700:MIRN1246 microRNA, human