Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment             epithelial cells.
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.
Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan ROC.
Chien-Neng
CN
Kuo
Chung-Yi
CY
Chen
Chien-Hsiung
CH
Lai
Li-Ju
LJ
Lai
Pei-Chen
PC
Wu
Chia-Hui
CH
Hung
Ching-Hsein
CH
Chen
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056741:Cyclin D / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D056741:Cyclin D; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000068258:Bevacizumab; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6