Vilà Natàlia, Coblentz Jacqueline, Moreira-Neto Carlos, Bravo-Filho Vasco, Zoroquiain Pablo, Burnier Miguel N
Henry C. Witelson Ocular Pathology Laboratory, Montreal, Que., Canada.
Ophthalmic Res. 2017;57(1):48-53. doi: 10.1159/000449252. Epub 2016 Oct 15.
To determine whether pretreatment of retinal pigmented epithelial (RPE) cells with lutein can affect the response of cells to bevacizumab therapy.
One human RPE cell line (ARPE-19) was used for all experiments. The cells were treated with lutein in different concentrations (0.01, 0.1, 1, 10, or 100 μg/ml). After 24 h, all plates were treated with bevacizumab (0.25 mg/ml). Media were harvested 24 h later for sandwich ELISA-based angiogenesis arrays. A Quantibody Human Angiogenesis Array was used in order to quantify the secretion of the following 10 proangiogenic cytokines: angiogenin, ANG2, EGF, bFGF, HB-EGF, PDGF-BB, leptin, PIGF, HGF and VEGF.
Treatment with bevacizumab alone led to a significant decrease in VEGF, as well as a significant increase in angiogenin and bFGF. Pretreatment with 0.1 and 1.0 μg/ml of lutein led to significant decreases in both bFGF and angiogenin following treatment with bevacizumab compared to bevacizumab treatment alone. Lutein alone did not modify the secretion of proangiogenic cytokines.
Pretreatment of human RPE cells in culture with specific doses of lutein prior to bevacizumab treatment mitigated the increase in bFGF and angiogenin caused by bevacizumab monotherapy.
确定用叶黄素预处理视网膜色素上皮（RPE）细胞是否会影响细胞对贝伐单抗治疗的反应。
所有实验均使用一种人RPE细胞系（ARPE - 19）。细胞用不同浓度（0.01、0.1、1、10或100μg/ml）的叶黄素处理。24小时后，所有平板用贝伐单抗（0.25mg/ml）处理。24小时后收集培养基用于基于夹心ELISA的血管生成阵列检测。使用定量抗体人血管生成阵列来定量以下10种促血管生成细胞因子的分泌：血管生成素、ANG2、表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、肝素结合表皮生长因子（HB - EGF）、血小板衍生生长因子BB（PDGF - BB）、瘦素、胎盘生长因子（PIGF）、肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）。
单独使用贝伐单抗治疗导致VEGF显著降低，以及血管生成素和bFGF显著增加。与单独使用贝伐单抗治疗相比，用0.1和1.0μg/ml叶黄素预处理导致在用贝伐单抗治疗后bFGF和血管生成素均显著降低。单独使用叶黄素未改变促血管生成细胞因子的分泌。
在贝伐单抗治疗前用特定剂量的叶黄素预处理培养的人RPE细胞，可减轻贝伐单抗单药治疗引起的bFGF和血管生成素的增加。
