title: FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells.
abstract: The Wnt signaling pathway is activated in hepatocellular carcinoma (HCC). This study investigated the effects of FH535, an inhibitor of the Wnt signaling pathway, on the proliferation and motility of HCC cells. HLF cells and PLC/PRF/5 cells, HCC cells, were subjected to 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay with the addition of FH535. RNA was isolated from the cells and subjected to real-time quantitative PCR. Hematoxylin and eosin (H&E) staining was performed to analyze apoptosis. A scratch assay was performed to analyze cell motility. Cell proliferation significantly decreased (P<0.05). The expression levels of cyclin D1 significantly decreased in both cell lines (P<0.05). Pyknotic nuclei were observed in the cells cultured with FH535 (50 µM). In the scratch assay, the distance between the growing edges of cells and the scratched line significantly decreased with the addition of FH535 at 50 µM (P<0.05). The expression levels of matrix metalloproteinase 9 significantly decreased at 50 µM (P<0.05). FH535 suppressed the proliferation of HCC cells by downregulating the expression of cyclin D1 and by inducing apoptosis. Further, it suppressed cell motility by downregulating the expression of matrix metalloproteinase.
authors.affiliation: Department of Gastroenterology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tomizawa
authors.affiliation: Department of Radiology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.
authors.forename: Fuminobu
authors.initials: F
authors.lastname: Shinozaki
authors.affiliation: Department of Neurology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Motoyoshi
authors.affiliation: Department of Rheumatology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Pediatrics, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Neurosurgery, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284-0003, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishige
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage*; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: C575430:FH535; D013449:Sulfonamides; D019938:Cyclin D1; D020780:Matrix Metalloproteinase 9