Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle

Raluca Rusovici, Chirag J Patel, Kakarla V ChalamUniversity of Florida, Department of Ophthalmology, Jacksonville, FL, USABackground: The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of co...

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Autores principales:	Rusovici R, Patel CJ, Chalam KV
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/fe25b94aa8bb4a6685f11c565a4a97ed
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spelling	oai:doaj.org-article:fe25b94aa8bb4a6685f11c565a4a97ed2021-12-02T08:42:46ZBevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle1177-54671177-5483https://doaj.org/article/fe25b94aa8bb4a6685f11c565a4a97ed2013-02-01T00:00:00Zhttp://www.dovepress.com/bevacizumab-inhibits-proliferation-of-choroidal-endothelial-cells-by-r-a12207https://doaj.org/toc/1177-5467https://doaj.org/toc/1177-5483Raluca Rusovici, Chirag J Patel, Kakarla V ChalamUniversity of Florida, Department of Ophthalmology, Jacksonville, FL, USABackground: The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established.Methods: Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1&ndash;2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy.Results: Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P &lt; 0.01) and a decrease in the G0/G1 phase population (55.08%, P &lt; 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P &lt; 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P &lt; 0.01]). The increase in GO/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent.Conclusion: Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.Keywords: bevacizumab, age-related macular degeneration, vascular endothelial growth factor.Rusovici RPatel CJChalam KVDove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2013, Iss default, Pp 321-327 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ophthalmology RE1-994
spellingShingle	Ophthalmology RE1-994 Rusovici R Patel CJ Chalam KV Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
description	Raluca Rusovici, Chirag J Patel, Kakarla V ChalamUniversity of Florida, Department of Ophthalmology, Jacksonville, FL, USABackground: The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established.Methods: Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1&ndash;2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy.Results: Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P &lt; 0.01) and a decrease in the G0/G1 phase population (55.08%, P &lt; 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P &lt; 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P &lt; 0.01]). The increase in GO/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent.Conclusion: Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.Keywords: bevacizumab, age-related macular degeneration, vascular endothelial growth factor.
format	article
author	Rusovici R Patel CJ Chalam KV
author_facet	Rusovici R Patel CJ Chalam KV
author_sort	Rusovici R
title	Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
title_short	Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
title_full	Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
title_fullStr	Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
title_full_unstemmed	Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
title_sort	bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/fe25b94aa8bb4a6685f11c565a4a97ed
work_keys_str_mv	AT rusovicir bevacizumabinhibitsproliferationofchoroidalendothelialcellsbyregulationofthecellcycle AT patelcj bevacizumabinhibitsproliferationofchoroidalendothelialcellsbyregulationofthecellcycle AT chalamkv bevacizumabinhibitsproliferationofchoroidalendothelialcellsbyregulationofthecellcycle
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Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle

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