Carcinogenesis Advance Access first published online on April 13, 2007
This version published online on April 17, 2007
Carcinogenesis, doi:10.1093/carcin/bgm091
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The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic animal model of uveal melanoma
The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, Montreal, PQ, Canada
Correspondence to Jean-Claude Marshall The Henry C. Witelson Ophthalmic Pathology Laboratory, 3775 University St., Lyman Duff Building, Room 216, H3A 2B4, Montreal, Quebec, Canada, Phone: (514) 398-3456 ext 4, Fax: (514) 398-5728. E-mail: jeanclaude.marshall{at}gmail.com
The expression of cyclooxygenase-2 (COX-2) has been reported as an indicator of poor prognosis in a wide variety of human tumours, including colon, breast and uveal melanoma. COX-2 inhibitors have shown promise in controlling the malignancy of several types of tumours. Previous studies have demonstrated the efficacy of a COX-2 inhibitor on the proliferation rates of human uveal melanoma cells. The goal of this experiment was to investigate the efficiency of Nepafenac, a topically administered COX-2 inhibitor, in a rabbit model of uveal melanoma. The animals were divided into two groups of 14 animals for the duration of the 12-week experiment. One animal per group was sacrificed each week to evaluate disease progression and for histopathological studies. The experimental group received drops containing 0.3% Nepafenac solution. Intraocular tumor growth was evaluated weekly by fundoscopic examination and each animal was weighed prior to examination. Blood samples were taken weekly from all rabbits to detect circulating malignant cells throughout the experiment. After the second week of inoculation, the experimental group weighed significantly more than the control group. The control group developed more intraocular tumors and presented with metastases and higher detectable levels of circulating malignant cells before the treated group. These results indicate that the topical administration of a COX-2 inhibitor delayed the progression of this malignancy in our animal model. A clinical trail using an anti-COX-2 inhibitor for patients with uveal melanoma should be considered.
The figures have been added in this version.
Received February 1, 2007; revised March 15, 2007; accepted March 30, 2007.