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Weiwei Chen, Jiao Wang, Dan-Ning Hu, Dongsheng Yan; Epigenetic Drugs Inhibit Uveal Melanoma Cell Proliferation and Cell Cycle Progression. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5312.
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© ARVO (1962-2015); The Authors (2016-present)
Emerging evidence indicates that epigenetic drugs, such as DNA hypomethylating agents and histone deacetylase (HDAC) inhibitors have substantial efficacy in treating some cancers. Their effects on uveal melanoma, however, are largely unknown. To deal with this question, we determined the effects of four epigenetic drugs on uveal melanoma cell proliferation and apoptosis. The drugs used include two hypomethylating agents and two HDAC inhibitors.
The uveal melanoma cell lines M23 and SP6.5 were cultured and treated, respectively, with 5-azacytidine and decitabine, two hypomethylating agents approved by the FDA for the treatment of myelodysplastic syndrome, SAHA and romidepsin, two HDAC inhibitors approved by the FDA for cancer therapy in treating T-cell lymphomas. The MTS assay measured uveal melanoma cell proliferation. Flow cytometry analyzed cell cycle progression. Caspase 3/7 assays examined cell apoptosis.
Uveal melanoma cell proliferation was dramatically inhibited after treatment with each of these four epigenetic drugs. 5-azacytidine, SAHA and romidepsin induced G1-arrest, while decitabine blocked the G2 phase. All of these epigenetic drugs did had no obvious effects on cell apoptosis.
Our results imply that these epigenetic drugs may be developed as potential agents in uveal melanoma treatment.
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