Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells

Kuo,Chien-Neng; Chen,Chung-Yi; Lai,Chien-Hsiung; Lai,Li-Ju; Wu,Pei-Chen; Hung,Chia-Hui; Chen,Ching-Hsein

doi:10.3892/mmr.2012.986

Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells

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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Affiliations: Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan R.O.C., Department of Medical Laboratory Science and Biotechnology, School of Medicine and Health Sciences, Fooyin University, Kaohsiung 83102, Taiwan R.O.C., Chang Gung University College of Medicine and Chang Gung University of Science and Technology, Taiwan R.O.C. , Department of Dermatology, Chang Gung Memorial Hospital, Chiayi, Taiwan R.O.C., Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan 60004, R.O.C.
Published online on: July 11, 2012 https://doi.org/10.3892/mmr.2012.986
Pages: 701-704

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Abstract

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.

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