Antifibrotic activity of bevacizumab on human Tenon's fibroblasts in vitro.
Invest Ophthalmol Vis Sci
; 51(12): 6524-32, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20574016
ABSTRACT
PURPOSE:
To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenon's capsule fibroblasts (HTFs) in an in vitro model of wound healing.METHODS:
Fibroblasts were cultured in RPMI media, and bevacizumab was administered at a concentration ranging from 0.25 to 12.5 mg/mL. Fibroblast viability and cell death were assessed using the MTT colorimetric assay, lactate dehydrogenase assay, BrdU assay, and live/dead assay. Fibroblast contractility was assessed in floating collagen gels. Morphologic changes were assessed by transmission electron microscopy. Antifibrosis activities were compared with 5-fluorouracil.RESULTS:
Bevacizumab induced a significant dose-related reduction of HTF cell number at 12.5 mg/mL at 72 hours (P < 0.05). Under serum-free conditions, bevacizumab induced significant fibroblast cell death at concentrations greater than 7.5 mg/mL (P < 0.05). Bevacizumab caused a moderate inhibition of fibroblast gel contraction from baseline (P < 0.05). Scanning electron microscopy revealed marked vacuolization in bevacizumab-treated fibroblasts.CONCLUSIONS:
Bevacizumab disrupted fibroblast proliferation, inhibited collagen gel contraction ability, and induced fibroblast cell death at concentrations greater than 7.5 mg/mL in serum-free conditions. These results demonstrated that bevacizumab inhibited a number of fibrosis activities in culture. These activities may underpin the antifibrosis effect proposed in vivo.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Inibidores da Angiogênese
/
Fator A de Crescimento do Endotélio Vascular
/
Proliferação de Células
/
Cápsula de Tenon
/
Fibroblastos
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article