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L. R. Santos, J.-C. Marshall, R. J. Barry, D. Abourbih, M. Orellana, M. N. Burnier, Jr.; The Effect of Gleevec® on the Proliferation, Invasive Ability and Radiosensitivity of Retinoblastoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1592.
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Retinoblastoma (Rb) is the most common malignant intra-ocular tumor in childhood and the most common retinal tumor. Despite success in the treatment of this malignancy, there is a significant incidence of recurrence, metastatic disease and subsequent death in affected individuals. Imatinib mesylate (Gleevec®, Novartis Pharma) is a small molecule inhibitor of C-Abl, platelet-derived growth factor (PDGF) receptor and C-Kit tyrosine kinases. Imatinib has been approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors and is under investigation for the therapy of several other malignant tumors. The aim of this study is to evaluate the potential effect of Gleevec® on the proliferation and invasive abilities of two human retinoblastoma (Rb) cell lines. Furthermore the ability to radio-sensitize Rb cells was evaluated.
Two human Rb cell lines (WERY-RB and Y79) were cultured under normal growth conditions. An MTT-based proliferation assay was used to compare Rb cell growth with and without exposure to 10 µM Imatinib. In addition an invasion assay was performed with the same dose of Imatinib. The cells were also irradiated with graded dosages of 0, 2, 4, 6, 8 and 10 Gy with and without Imatinib and their proliferations rates were analyzed. The Student’s t-test was used to compare the in vitro proliferation rates of Rb cell lines and an ANOVA test was used to determine the differences in the invasive ability.
When Imatinib was added to both cell lines a statistically significant (p<0.05) reduction in proliferation and invasive ability were observed. Exposure to Imatinib also significantly increased the radiosensitivity of both Rb cell lines, decreasing their proliferation rates after radiation as compared to the control Rb cells receiving the same amount of radiation.
Imatinib mesylate decreased the proliferation and invasive abilties of both retinoblastoma cell lines. The radiosensitivity of both retinoblastoma cell lines were increased by the exposure to Imatinib. These results indicate that Gleevec® may be useful as an adjuvant treatment in retinoblastoma patients, especially those considered for radiation therapy. A clinical trial should be undertaken to evaluate the effect of this particular drug on retinoblastoma patients.
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