Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt

Authors

  • Bing Liu,

    1. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, PR China
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  • Zhong-li Shi,

    1. Institute of Orthopedic Research, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
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  • Jie Feng,

    1. Institute of Orthopedic Research, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China
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  • Hui-min Tao

    Corresponding author
    1. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, PR China
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Corresponding author. Fax: +86 571 8778 3578. huimintao_zrgk@163.com

Abstract

Cyclooxygenase-2 (COX-2), involved in the inhibition of apoptosis and, the potentiation of cell growth, is frequently overexpressed in human malignancies including osteosarcoma (OS). We have attempted to identify the anti-proliferation of celecoxib, a selective COX-2 inhibitor, and the combination of celecoxib and cisplatin in MG-63 cells, and to explore the potential molecular mechanisms involved. MG-63 cells were treated with the combination of celecoxib and cisplatin or either agent alone for 48 h in serum-supplemented medium. Celecoxib caused G1 phase arrest and significantly inhibited cell growth, as well as potentiating cisplatin-induced apoptosis. The effect was dose-dependent, and apoptotic changes such as DNA fragments and apoptotic bodies were observed. However, downregulation of COX-2 did not occur in cells treated with celecoxib. Phosphoinositide-3-kinase (PI3K)/Akt, survivin, bcl-2 were significantly downregulated in cells treated with the combination of celecoxib and cisplatin, and decreased survivin and bcl-2 levels were found in cells with wortmannin, a specific PI3K inhibitor. Moreover, the decreased expressions of procaspase-9, procaspase-3 and cleaved PARP-1 were detected by Western blot analysis. Therefore, celecoxib exerts its anti-tumor activities through COX-2-independent mechanisms, which may be PI3K/Akt-dependent, and survivin and bcl-2-related. PI3K may be at the center of the celecoxib effects, which play an essential role in the regulation of survivin and Bcl-2.

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