Document Detail


Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells.
MedLine Citation:
PMID:  22798045     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bevacizumab, a recombinant humanized monoclonal antibody, binds vascular endothelial growth factor (VEGF) and inhibits its interaction with receptors found on endothelial cells. Bevacizumab has been increasingly used as an off-label treatment for exudative age-related macular degeneration (AMD). Whether or not bevacizumab is capable of arresting the growth of human retinal pigment epithelial cells remains to be clarified. In this study, flow cytometry was used to evaluate whether bevacizumab markedly induced the G1/S phase arrest. The G1/S phase cycle-related protein analysis demonstrated that the expression of cyclin-dependent kinase (CDK)2, 4 and 6 and of cyclin D and E, as well as the phosphorylation of retinoblastoma tumor suppressor protein (ppRB) production were found to be markedly reduced by bevacizumab. By contrast, the protein levels of p53, p16, p21 and p27 were increased in bevacizumab-treated ARPE-19 cells (a human retinal pigment epithelial cell line). These events of G1/S arrest induced by bevacizumab in ARPE-19 cells suggest that a preventive effect of bevacizumab exists in AMD.
Authors:
Chien-Neng Kuo; Chung-Yi Chen; Chien-Hsiung Lai; Li-Ju Lai; Pei-Chen Wu; Chia-Hui Hung; Ching-Hsein Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-11
Journal Detail:
Title:  Molecular medicine reports     Volume:  6     ISSN:  1791-3004     ISO Abbreviation:  Mol Med Rep     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-08-16     Completed Date:  2013-03-14     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  101475259     Medline TA:  Mol Med Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  701-4     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan ROC.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / pharmacology*
Antibodies, Monoclonal, Humanized / pharmacology*
Cell Survival / drug effects
Cells, Cultured
Cyclin D / metabolism
Cyclin E / metabolism
Cyclin-Dependent Kinase 2 / metabolism
Cyclin-Dependent Kinase 4 / metabolism
Cyclin-Dependent Kinase 6 / metabolism
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
G1 Phase Cell Cycle Checkpoints / drug effects*
Humans
Macular Degeneration / drug therapy,  metabolism,  pathology
Phosphorylation
Retinal Pigment Epithelium / cytology,  metabolism*
Retinoblastoma Protein / metabolism
S Phase Cell Cycle Checkpoints / drug effects*
Tumor Suppressor Protein p53 / metabolism
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/Cyclin D; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 2S9ZZM9Q9V/bevacizumab; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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