title: GSK-3 inhibitor inhibits cell proliferation and induces apoptosis in human osteosarcoma cells.
abstract: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that functions in numerous signaling pathways initiated by diverse stimuli. The functions of GSK-3 in cancer differ depending on cell type. In the present study, we examined the effects of a specific GSK-3 inhibitor on the regulation of osteosarcoma cell proliferation and apoptosis. Immunohistochemical analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) were performed to determine the expression pattern of GSK-3 in human osteosarcoma cells. We used the MTS assay, western blotting, measurement of single-stranded DNA and morphological analyses to study the effects of a GSK-3 inhibitor, SB216763 on osteosarcoma cell proliferation and survival. We detected an increase in mRNA expression of GSK-3 and aberrant nuclear accumulation of GSK-3 in the osteosarcoma cells. Pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of osteosarcoma cells. Inhibition of GSK-3 resulted in a decreased expression of Bcl-2 and a subsequent increase in osteosarcoma cell apoptosis via the mitochondrial pathway. The present study demonstrated that GSK-3 activity is critical for tumorigenicity and cell survival in osteosarcoma cells. Our findings suggest that GSK-3 is a potential therapeutic target for the treatment of human osteosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakamura
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamagami
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Horie
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Fukuoka
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D038362:Glycogen Synthase Kinase 3