The Cyclooxygenase-2 Selective Inhibitor Celecoxib Suppresses Proliferation and Invasiveness in the Human Oral Squamous Carcinoma

摘要

Cyclooxygenease-2 (COX-2) expression is a critical factor in inflammation, and plays an important role in defense against ex ogenous stimuli, while overexpression of COX-2 causes cells to exhibit changes in tumor phenotype. This article attempted to determine the mechanisms underlying the chemopreventive effects of celecoxib on cel lular level events, in order to characterize the effects of celecoxib with regard to human oral squamous cell carcinoma (OSCC) cell growth and invasion/migration. In order to determine COX-2 expression levels, we used an OSCC cell line established from surgically resected speci mens of an untreated primary OSCC of the tongue, and used reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses with anti-COX-2 monoclonal antibodies. The YD-10B cells rep resented a highly invasive OSCC cell line, which was found to express the COX-2 protein. Celecoxib inhibited the growth of this OSCC cell line, in a time- and dose-dependent manner. This reduction in cell prolifera tion was associated with the upregulation of the cyclin-dependent kinase (CDK) inhibitors, p27. In addition, 10 uM celecoxib inhibited cell inva sion/migration through the type I collagen matrix by ～40% within 24 h. The results of zymography reveal that, in the presence of 10 μL celecoxib, both MMP-2 and MMP-9 enzyme activity decreased by ～30-40%. The current in vitro study indicated that the inhibition of proliferation and invasion/migration in OSCC cell line by the COX-2-specific inhibitor, celecoxib, results in anticancerous effects via a variety of cellular and molecular mechanisms. This article also supports the notion that the COX-2 inhibitor may be useful in the inhibition and/or prevention of metastasis.