Erlotinib has tumor inhibitory effect in human retinoblastoma cells

Abstract

AimIn this study, we explored the effect of erlotinib on the development of retinoblastoma (RB) cells both in vitro and in vivo. MethodRB cell lines, Y79 and WERI cells were treated with various concentrations of erlotinib in vitro to assess their cytotoxic profiles. In vitro proliferation, cell-cycle transition and migration were compared between RB cells treated with erlotinib and cells without erlotinib treatment. In in vivo tumorigenicity assay, mice were injected with Y79 cells and orally fed with erlotinib for 28days. The effect of erlotinib on in vivo tumor grafts was then assessed. Western blot analysis on EGFR, ERK, AKT proteins and their phosphorylated proteins was also performed to assess molecular signaling pathways of associated with erlotinib in RB cells. ResultsIn vitro erlotinib treatment induced cytotoxicity in Y79 and WERI cells in dose-dependent manner. While Y79 and WERI cells were treated with erlotinib close to EC50 concentrations for 3days, RB proliferation, cell-cycle transition and migration were all significantly inhibited. In in vivo tumorigenicity assay, oral induction of erlotinib also dramatically reduced the growth of Y79 tumor grafts. Western blot demonstrated that, in in vitro RB cells, erlotinib did not alter the protein expression levels of EGFR, ERK or AKT, but significantly reduced the expressions of phosphorylated EGFR, ERK and AKT proteins. ConclusionErlotinib was shown to have tumor suppressive effect on RB growth in vitro and in vivo, possibly through the inhibition on EGFR, ERG/AKT signaling pathways.