Amfenac increases the radiosensitivity of uveal melanoma cell lines.
OBJECTIVE
To evaluate the proliferation rates of five human uveal melanoma (UM) cell lines after treatment with amfenac, a cyclooxygenase (COX)-2 inhibitor, and subsequent radiation exposure.


METHODS
Five human UM cell lines (92.1, SP6.5, MKT-BR, OCM-1, and UW-1) and one human fibroblast cell line (BJ) were incubated with amfenac. Treated and non-treated cell lines were then exposed to various doses of gammaradiation: 0, 2, 4, 6, and 8 Gy. Sulphorhodamine-B assay was used to assess proliferation rates 48 h post-radiation.


RESULTS
Treatment of UM cell lines with amfenac prior to radiation led to a marked reduction in proliferation rates. This difference was statistically significant in all cell lines at every radiation dose (P<0.005), with the exception of 92.1 at 2 Gy (P=0.157). Fibroblasts treated with amfenac showed significantly higher proliferation rates after 2 and 8 Gy, with no significant differences at 0, 4, and 6 Gy.


CONCLUSIONS
The radiosensitivity of UM cell lines was increased by the administration of amfenac, the active metabolite of nepafenac. There appears to be a radioprotective effect of amfenac on human fibroblasts. The topical administration of nepafenac may decrease tumour recurrence and radiation-induced complications while broadening the indications for radiotherapy by treating larger tumours.
Department of Ophthalmology and Pathology, The McGill University Health Center, Montreal, Canada. bruno.mtl@gmail.com
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Fernandes
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Marshall
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Di Cesare
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Logan
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Maloney
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Burnier
D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000532:radiotherapy; D010648:Phenylacetates / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014604:Uveal Neoplasms / Q000473:pathology* / Q000532:radiotherapy
D052246:Cyclooxygenase 2 Inhibitors; D010648:Phenylacetates; D011838:Radiation-Sensitizing Agents; C014285:amfenac