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B. F. Fernandes, J.-C. Marshall, S. di Cesare, P. Logan, S. Bakalian, M. N. Burnier, Jr.; The Effect of a COX-2 Inhibitor on the Radiosensitivity of Uveal Melanoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4752.
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Radiotherapy has become the preferred form of treatment for primary uveal melanoma. Although success rates are high, a significant number of cases end up being enucleated, either due to treatment failure or radiation-associated complications. Cyclooxygenase-2 (COX-2) inhibitors have already been described as radiosensitizers in lung cancer. The aim of this study was to evaluate the proliferation rates of five different melanoma cell lines treated with Amfenac, a COX-2 inhibitor, after delivering increasing doses of radiation.
Five human uveal melanoma cell lines (92.1, SP6.5, MKT-BR, OCM-1 and UW-1) were incubated with 150 nM concentration of Amfenac, the active metabolite of Nepafenac, a COX-2 inhibitor. Cells were seeded at a concentration of 500,000 cells per ml in micro-petridishes and allowed to incubate overnight. The cells were then exposed to increasing doses of gamma irradiation (Gamma Cell 1000): 0, 2, 4, 6 and 8 Gy. A set of dishes per cell line without Amfenac were kept as controls and were exposed to the same graded doses of radiation. Post irradiation, all cells from the micro-petridishes were trypsinised, washed in 5% FBS RPMI solution and spun down for 5 minutes at 3000g. Cells were then seeded in a 96 well plate format at a concentration of 5000 cells per well and left to incubate at 37oC for 48h. The Sulforhodamine-B assay kit (TOX-6, Sigma-Aldrich Co., St. Louis, Missouri, USA) was used to assess the proliferation rates. The proliferation assay was done in triplicate per exposure condition and the Student T-test was used to test for differences. A p-value of less than 0.05 was considered statistically significant.
The effect of radiation was significantly more pronounced on those cell lines treated with Amfenac. The difference in the proliferation rates between treated and non-treated cell lines was statistically significant in all cell lines and radiation doses (p<0.05), except for the 92.1 cell line using 2 Gy (p=0.157).
To the best of our knowledge this is the first evidence of a drug capable of enhancing the effects of radiation in uveal melanoma cell lines. The radiosensitivity was increased by the administration of amfenac, the active metabolite of Nepafenac. The topical administration of this drug to uveal melanoma patients, before radiotherapy, may increase success rates for local tumor control and broaden the indications for radiotherapy by treating larger tumors.
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