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S. Bakalian, E. Antecka, D. Faingold, C. Martins, E. Castiglione, M. N. Burnier, Jr.; Topical COX-2 Inhibitor Decreases the Expression of C-Met in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):63.
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Expression of C-Met has been shown to be correlated with mortality in uveal melanoma (UM) patients. In addition, the expression of cyclooxygenase-2 (COX-2) has been reported to be an indicator of poor prognosis in a wide variety of tumors, including UM. Previous work demonstrated that a COX-2 inhibitor (Nepafenac) could delay the progression of UM, including development of metastatic disease, in a rabbit model. The aim of this study was to investigate the expression of C-Met in the intraocular tumors of non-treated and Nepafenac-treated animals. Furthermore, we evaluated the expression of C-Met mRNA in non-treated and treated human UM cell lines.
Twenty-eight New Zealand albino rabbits were divided into two equal groups. The experimental group received eye drops containing 0.3% Nepafenac solution while the control group received a placebo. Two drops were administered twice daily for the duration of the 12-week experiment. One animal per group was sacrificed each week for histopathological studies. Paraffin-embedded primary intraocular tumor sections from each of the 28 animals were immunostained with a C-Met monoclonal antibody. The immunostaining was evaluated semi-quantitatively based on staining extent and intensity. The expression levels of C-Met mRNA were also assessed in five human UM cell lines (92.1, OCM-1, SP6.5, MKT-BR, and UW-1) before and after treatment with Amfenac, the active metabolite of Nepafenac, using quantitative real-time PCR.
All intraocular tumors stained positive, to varying degrees for C-Met expression. The immunostaining was cytoplasmic in all samples. The intensity of immunostaining was significantly higher in the primary tumors of all non-treated rabbits when compared to the Nepafenac-treated group. All five human UM cell lines expressed different levels of C-Met mRNA, however, the expression was always higher in non-treated cell lines compared to treated cell lines. There was up to a four-fold decrease in the expression levels of C-Met mRNA after treatment with Amfenac.
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