Abstract
Purpose: :
The expression of cyclooxygenase–2 (COX–2) has been reported in wide variety of human tumours, including colon, breast and uveal melanoma as an indicator of poor prognosis. COX–2 inhibitors have shown promise in controlling the malignancy of several tumour types. Previous work has demonstrated the efficacy of a COX–2 inhibitor on the proliferation rates of human uveal melanoma cells. We aim to investigate the use of Nepafenac, a COX–2 inhibitor, in a rabbit model of uveal melanoma.
Methods: :
Twenty–eight albino rabbits were injected with 1x106 human uveal melanoma cells (92.1) into the suprachoroidal space of the eye. Animals were immunosuppressed using cyclosporin A throughout the 12 week long experiment. The animals were divided into two groups of 14 animals each. The control group received drops that contained only the vehicle. The experimental group received drops containing 0.3% Nepafenac solution. Each group was given two drops, twice daily. Intraocular tumor growth was evaluated weekly by fundoscopic examination and each animal was weighed at the same time. One animal was sacrificed per week, after the 2nd week, in order to evaluate progression of the disease. Upon necropsy tissue all organs were saved for histopathological examination.
Results: :
The initial weight of the rabbits was equal between both groups. Following the second week after inoculation the experimental group continued to have a significantly higher weight than the control group. At week ten, out of sixteen rabbits, 3 animals from the control group had presented with a large intraocular mass at the time of sacrifice, compared to only one from the experimental group. Three rabbits from the control group, sacrificed at weeks 8, 9 and 10, presented with large metastatic lesions of the lungs. No rabbits from the experimental group have presented with large metastatic lesions at weeks 8, 9 and 10. Histopathological examination using serial sections of lung and liver as well as immunohistochemical markers revealed lung metastatic lesions in all control animals after the 4th week of the experiment. The experimental group revealed micrometastasis in animals sacrificed following the 8th week of the experiment.
Conclusions: :
The results indicate that a COX–2 inhibitor (Nepafenac) has an effect on the progression of human uveal melanoma in an immunosuppressed rabbit model. The use of this inhibitor has delayed the progression of the ocular tumour as well as the development of metastatic disease in this animal model. A clinical trail using an anti–COX–2 inhibitor for patients with uveal melanoma should be considered.
Keywords: melanoma • oncology • drug toxicity/drug effects