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K. M. Oliver, IV, S. Di Cesare, J.-C. Marshall, P. Logan, D. Faingold, M. N. Burnier, Jr.; Effects of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG), Imatinib, and Amfenac on the Cellular Proliferation of 5 Human Uveal Melanoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4770.
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To determine whether uveal melanoma cells are sensitive to the cytotoxic effects of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG), Imatinib (Gleevec), and Amfenac (Nepafenac) alone or in combination.
Five uveal melanoma cell lines were used in the study. These cell lines in order of increasing metastatic potential are 92.1, SP6.5, MKT-BR, OCM-1, UW-1. All 5 cells lines were grown in culture and were subsequently exposed to each of the 3 agents separately and in combination: imatinib and 17-AAG (group 1), 17-AAG and amfenac (group 2), and imatinib and amfenac (group 3) at varying concentrations of 10-0.001ug/ml. A control sample of all 5 cell lines which had no exposure to any of the 3 agents was also cultured. After 48 hrs in culture, the cellular proliferation rates were measured using a Sulfurhodamine-B based proliferation assay.
A significant decrease in proliferation (p<0.05) of all 5-cell lines was seen with both imatinib and 17-AAG alone. In group 1, the co-treatment of cells with imatinib and 17-AAG resulted in a larger decrease in proliferation than with either drug alone. In group 2, the exposure of cells to amfenac resulted in a sensitization to 17-AAG, prolonging the dose response of our cells to this HSP90 inhibitor. The exposure of cells to imatinib and amfenac in group 3 showed a small additive effect.
Therapy with imatinib and 17-AAG alone resulted in decreased cellular proliferation of 5 uveal melanoma cell lines. Combined treatment with imatinib and 17-AAG was more effective in reducing cellular proliferation than either drug alone. This group showed the greatest decrease in proliferation rate compared to the other tested combinations. These results suggest that the combination of these two agents has an additive or synergistic effect and should be further investigated for their potential as a future therapy in UM patients.
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