GSK-3 inhibitor inhibits cell proliferation and induces apoptosis in human osteosarcoma cells

Nishimura,Hideki; Nakamura,Osamu; Yamagami,Yoshiki; Mori,Masaki; Horie,Ryosuke; Fukuoka,Natsuko; Yamamoto,Tetsuji

doi:10.3892/or.2016.4565

GSK-3 inhibitor inhibits cell proliferation and induces apoptosis in human osteosarcoma cells

Authors:
- Hideki Nishimura
- Osamu Nakamura
- Yoshiki Yamagami
- Masaki Mori
- Ryosuke Horie
- Natsuko Fukuoka
- Tetsuji Yamamoto
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Affiliations: Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
Published online on: January 15, 2016 https://doi.org/10.3892/or.2016.4565
Pages: 2348-2354

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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.

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