Effects of Antiangiogenic Drugs on Expression Patterns of Epigenetic Pathway Genes
Copyright 2018, SLACK Incorporated.
| Veröffentlicht in: | Ophthalmic surgery, lasers & imaging retina. - 2013. - 49(2018), 10 vom: 15. Okt., Seite S29-S33 |
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| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2018
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| Zugriff auf das übergeordnete Werk: | Ophthalmic surgery, lasers & imaging retina |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Angiogenesis Inhibitors Recombinant Fusion Proteins aflibercept 15C2VL427D RNA 63231-63-0 Receptors, Vascular Endothelial Growth Factor EC 2.7.10.1 mehr... |
| Zusammenfassung: | Copyright 2018, SLACK Incorporated. BACKGROUND AND OBJECTIVE: To investigate the effects of antiangiogenic drugs on the transcription profile of acetylation genes in immortalized human retinal pigment epithelium cells (ARPE-19) in vitro MATERIALS AND METHODS: This in vitro study evaluated the effect of antiangiogenic drugs on the expression of histone acetylation genes on immortalized ARPE-19 cell cultures. ARPE-19 cells were cultured, plated, and treated for 24 hours with aflibercept (Eylea; Regeneron, Tarrytown, NY), ranibizumab (Lucentis; Genentech, South San Francisco, CA), or bevacizumab (Avastin; Genentech, South San Francisco, CA) at one (1×) or two times (2×) the concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated, and real-time quantitative reverse transcription polymerase chain reaction analysis was performed on individual samples to quantify expression levels of genes associated with epigenetic acetylation pathways: histone acetyltransferase 1 (HAT1) and histone deacetylases 1, 6, and 11 (HDAC1, HDAC6, and HDAC11). Differences in cycle thresholds (ΔΔCts) were obtained, and folds were calculated using the formula 2^ΔΔCt. Main outcome measures were expression levels of candidate genes in treated versus untreated samples RESULTS: Compared with untreated cells, 1× ranibizumab-treated cells expressed higher levels of HDAC6, and 2× ranibizumab-treated cells expressed higher HDAC11 levels. Bevacizumab-treated (1×) cells had significant change in HDAC1, HDAC6, and HDAC11. In cultures treated with 2× bevacizumab, only HDAC11 expression levels were significantly affected compared with controls. Aflibercept-treated (1×) cells had changes in expression of HDAC1, HDAC6, and HDAC11. At 2× concentration, only HDAC11 was significantly changed CONCLUSION: Our results show that antiangiogenic drugs can affect the transcription profile of genes regulating the histone acetylation status in ARPE-19 cells in vitro. This finding may have an implication in differential patient response to anti-vascular endothelial growth factor therapy by means of possible interactions between treatment and patient's epigenomic profile. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S29-S33.] |
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| Beschreibung: | Date Completed 20.03.2019 Date Revised 20.03.2019 published: Print Citation Status MEDLINE |
| ISSN: | 2325-8179 |
| DOI: | 10.3928/23258160-20180814-05 |