The effect of imatinib mesylate on the proliferation, invasive ability, and radiosensitivity of retinoblastoma cell lines

Abstract

Purpose Our aim was to evaluate the potential effect of imatinib mesylate (IM), a small molecule that specifically inhibits the tyrosine quinase receptors, on the proliferation and invasive abilities of two human retinoblastoma (Rb) cell lines. Furthermore, the ability of IM to radiosensitize Rb cells was evaluated. the potential targets of IM (C-kit, PDGRF-alpha and -beta, and c-Abl) were also investigated in these cell lines.Methods Two human Rb cell lines (WERI-RB-1 and Y79) were cultured under normal growth conditions. An MTT-based proliferation assay and a Matrigel invasion assay were performed with and without exposure to 10 mu M of IM. the cells were also irradiated with graded dosages of 0, 2, 4, 6, 8, and 10 Gy with and without IM and their proliferations rates were analyzed. Western blot and immunocytochemical analysis of cytospins were performed to evaluate the expression of C-kit, PDGRF-alpha and -beta, and c-Abl.Results When IM was added to both cell lines a statistically significant (P<0.05) reduction in proliferation and invasive ability were observed. Exposure to IM also significantly increased the radiosensitivity of both Rb cell lines. the c-Abl expression was strongly positive, PDGRF-alpha and -beta expression were also positive but the C-kit expression was negative in both cell lines.Conclusions These results indicate that Gleevec may be useful as an adjuvant treatment in Rb patients, specially those considered for radiation therapy. Eye (2013) 27, 92-99; doi:10.1038/eye.2012.231; published online 16 November 2012