title: The effect of imatinib mesylate on the proliferation, invasive ability, and radiosensitivity of retinoblastoma cell lines.
abstract: OBJECTIVE
  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-α and -β, 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 μM 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-α and -β, 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-α and -β 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.
authors.affiliation: Department of Ophthalmology and Pathology, The McGill University Health Center and Henry C Witelson Ocular Pathology Laboratory, Montreal, Quebec, Canada.
authors.forename: L R
authors.initials: LR
authors.lastname: de Moura
authors.forename: J-C
authors.initials: JC
authors.lastname: Marshall
authors.forename: S
authors.initials: S
authors.lastname: Di Cesare
authors.forename: B F
authors.initials: BF
authors.lastname: Fernandes
authors.forename: E
authors.initials: E
authors.lastname: Antecka
authors.forename: M N
authors.initials: MN
authors.lastname: Burnier
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012175:Retinoblastoma / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha