Celecoxib inhibits cell growth and modulates the expression of matrix metalloproteinases in human osteosarcoma MG-63 cell line

X. Zhou, X. Shi, K. Ren, G.-T. Fan, S.J. Wu, J.-N. Zhao

Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, China. zhaojianning_1957@126.com

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• Oncology

OBJECTIVE: The goal of this study was to determine the effect of celecoxib, a selective COX-2 inhibitor, on the growth inhibition of osteosarcoma and its potential anticancer mechanisms.

MATERIALS AND METHODS: Human osteosarcoma cell line MG-63 was used as a model. The inhibitory effect of celecoxib on cell proliferation was assessed by MTT assay. Flow cytometric analysis was used to detect the effects of celecoxib on cell cycle and apoptosis. Western blot analysis was used to detect the protein expression of RECK, matrix metalloproteinase (MMP)-2 and MMP-9 in celecoxib-treated MG-63 cells.

RESULTS: MTT assays showed that at a range of concentrations (0-80 µg/ml), celecoxib significantly inhibited the MG-63 cell proliferation in a time- and concentration-dependent manner. The half maximal inhibitory concentration (IC50) of celecoxib was 47.5 µg/ml for 24 h-treatment and 19.2 µg/ml for 48 h-treatment. Flow cytometric analysis demonstrated that treatment with 20 µg/ml celecoxib led to a significant cell cycle arrest at S-phase and an enhancement of apoptosis induction in MG-63 cells at 24 or 48h. Moreover, compared with 24 h-treatment, 48 h-treatment induced more S-phase arrest and apoptosis in MG-63 cells. Western blot analyses revealed that the expression of MMP-2 and MMP-9 was markedly down-regulated but RECK, an inhibitor of MMPs, was markedly up-regulated in MG-63 cells exposed to 20 µg/ml celecoxib for 24 or 48h. Furthermore, the effects of celecoxib on the expression of these molecules were more evident with the increase of treatment time.

CONCLUSIONS: Celecoxib inhibits the MG-63 cells proliferation through S-phase arrest and apoptosis induction. Celecoxib-induced down-regulation of MMP-2 and MMP-9 and up-regulation of RECK may contribute to the apoptosis induction and an alteration in local tumor microenvironment. These findings suggest that celecoxib may exert at least in part of its anticancer effects via up-regulation of RECK to inhibit the expression of MMP-2 and MMP-9.

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