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Raluca Rusovici, Chirag Patel, Kakarla V. Chalam; Effect of Bevacizumab on Cell Cycle of VEGF- Enriched Proliferating Choroidal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):788.
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To evaluate and quantify cell cycle changes in choroidal endothelial cells exposed to varying doses of Bevacizumab in the presence 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 choroidal cell cycle is not known.
Monkey choroidal endothelial RF/6A cells were treated with VEGF (50 ng/ml) and/or Bevacizumab (0.1-2 mg/ml) for 72h. Cell proliferation was measured with the WST-1 assay (Roche). Morphological changes were recorded by bright field microscopy of cells. Cell cycle changes in response to Bevacizumab were evaluated with Propidium Iodide (PI) staining.
Bevacizumab (1 mg/ml or 2 mg/ml) alone produced a 4.81% or 5.42% decrease in cell proliferation compared to controls, respectively (p=0.05). Bevacizumab (1 mg/ml or 2 mg/ml) and VEGF (50 ng/ml) produced a 12.1% or 10.2% decrease in cell proliferation compared to controls, respectively. VEGF (50 ng/ml) produced a 7.7% increase in cell proliferation compared to controls. The morphology of cells was unchanged after treatment with Bevacizumab and/or VEGF compared to controls.The percentage of Bevacizumab (2 mg/ml) and VEGF (50 ng/ml) - treated cells in the G0/G1 phase increased compared to controls (64% compared to 52% in controls; p=0.05). The percentage of Bevacizumab (1, 1.5 mg/ml)-treated cells in G2/M phase was similar to controls (23.03% and 23.04%, respectively; 21% in controls). The cell cycle effects of Bevacizumab on choroidal endothelial cells were dose-dependent.
Bevacizumab inhibits VEGF and stabilizes choroidal endothelial cells in G0/G1 phase compared to VEGF enriched cells.
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