title: Erlotinib has tumor inhibitory effect in human retinoblastoma cells.
abstract: OBJECTIVE
  In this study, we explored the effect of erlotinib on the development of retinoblastoma (RB) cells both in vitro and in vivo.
  
  
  METHODS
  RB 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.
  
  
  RESULTS
  In 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 EC50concentrations 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.
  
  
  CONCLUSIONS
  Erlotinib 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.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province clinical ophthalmology Institute, Nanchang, Jiangxi Province, 330006, China. Electronic address: yi.shao@aol.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province clinical ophthalmology Institute, Nanchang, Jiangxi Province, 330006, China; Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang Key Laboratory of Diabetes, Nanchang, Jiangxi Province, 330009, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian Province, 361102, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zong
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian Province, 361102, China.
authors.forename: Luowa
authors.initials: L
authors.lastname: Quyang
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian Province, 361102, China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province clinical ophthalmology Institute, Nanchang, Jiangxi Province, 330006, China. Electronic address: qiong-zhouzxc@sina.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province clinical ophthalmology Institute, Nanchang, Jiangxi Province, 330006, China. Electronic address: ppgang22@aol.com.
authors.forename: Chonggang
authors.initials: C
authors.lastname: Pei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D000069347:Erlotinib Hydrochloride
keywords: Cancer graft; Cancer migration; Cancer proliferation; Erlotinib; Retinoblastoma