Amfenac increases the radiosensitivity of uveal melanoma cell lines

Abstract

Purpose 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 gamma radiation: 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.McGill Univ, Dept Ophthalmol & Pathol, Ctr Hlth, Montreal, PQ H3A 2B4, CanadaHenry C Witelson Ocular Pathol Lab, Montreal, PQ H3A 2B4, CanadaUniversidade Federal de São Paulo, UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc