Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan ROC.
Mol Med Rep. 2012 Oct;6(4):701-4. doi: 10.3892/mmr.2012.986. Epub 2012 Jul 11.
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.
贝伐单抗是一种重组人源化单克隆抗体，可与血管内皮生长因子（VEGF）结合并抑制其与内皮细胞上受体的相互作用。贝伐单抗已越来越多地被用作渗出性年龄相关性黄斑变性（AMD）的标签外治疗药物。贝伐单抗是否能够阻止人视网膜色素上皮细胞的生长仍有待阐明。在这项研究中，流式细胞术用于评估贝伐单抗是否显著诱导 G1/S 期阻滞。G1/S 期周期相关蛋白分析表明，贝伐单抗显著降低了细胞周期蛋白依赖性激酶（CDK）2、4 和 6 以及细胞周期蛋白 D 和 E 的表达，以及视网膜母细胞瘤肿瘤抑制蛋白（ppRB）的磷酸化产物。相比之下，贝伐单抗处理的 ARPE-19 细胞（人视网膜色素上皮细胞系）中 p53、p16、p21 和 p27 的蛋白水平增加。贝伐单抗在 ARPE-19 细胞中诱导的这些 G1/S 期阻滞事件表明，贝伐单抗在 AMD 中存在预防作用。
