Document Detail

The effect of imatinib mesylate on the proliferation, invasive ability, and radiosensitivity of retinoblastoma cell lines.
MedLine Citation:
PMID:  23154488     Owner:  NLM     Status:  MEDLINE    
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-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.
L R de Moura; J-C Marshall; S Di Cesare; B F Fernandes; E Antecka; M N Burnier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-16
Journal Detail:
Title:  Eye (London, England)     Volume:  27     ISSN:  1476-5454     ISO Abbreviation:  Eye (Lond)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-10     Completed Date:  2013-06-04     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8703986     Medline TA:  Eye (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  92-9     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / pharmacology*
Benzamides / pharmacology*
Blotting, Western
Cell Line, Tumor / drug effects*,  metabolism,  radiation effects
Cell Proliferation / drug effects
Dose-Response Relationship, Radiation
Neoplasm Invasiveness
Piperazines / pharmacology*
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-kit / metabolism
Pyrimidines / pharmacology*
Radiation Tolerance / drug effects*
Receptor, Platelet-Derived Growth Factor alpha / metabolism
Retinal Neoplasms / drug therapy*,  metabolism
Retinoblastoma / drug therapy*,  metabolism
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzamides; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Pyrimidines; BKJ8M8G5HI/imatinib; EC Proteins c-kit; EC, Platelet-Derived Growth Factor alpha

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