Amfenac increases the radiosensitivity of uveal melanoma cell lines

Eye (Lond). 2008 May;22(5):701-6. doi: 10.1038/sj.eye.6703042. Epub 2007 Nov 30.

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 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.

MeSH terms

  • Cell Proliferation* / drug effects
  • Cell Proliferation* / radiation effects
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Humans
  • Melanoma / pathology*
  • Melanoma / radiotherapy
  • Phenylacetates / pharmacology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects
  • Uveal Neoplasms / pathology*
  • Uveal Neoplasms / radiotherapy

Substances

  • Cyclooxygenase 2 Inhibitors
  • Phenylacetates
  • Radiation-Sensitizing Agents
  • amfenac