Park J Y, Kwon B M, Chung S K, Kim J H, Joo C K
Department of Ophthalmology and Visual Science, Catholic Research Institute of Medical Science, The Catholic University of Korea, College of Medicine, Seoul, Korea.
Ophthalmic Res. 2001 Mar-Apr;33(2):111-6. doi: 10.1159/000055654.
To evaluate the inhibitory effect of the farnesyl transferase inhibitor 2'-O-benzoylcinnamaldehyde (CB 2'-ph) on proliferation and migration of vascular endothelial cells.
Bovine lens epithelial cells, bovine corneal endothelial cells, bovine keratocytes, bovine aortic endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) were treated with CB 2'-ph to determine its cell type specificity and antiproliferative effect. For inhibition of vascular endothelial cell growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-induced proliferation of HUVECs, these cells were treated with various concentrations of CB 2'-ph. To assess the proliferation, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used. The migration assay was also performed to determine the effect of CB 2'-ph on HUVECs. The distance of HUVEC outgrowth was measured from the scraped edge of a monolayer after treatment with CB 2'-ph concentrations of 0, 1.5 and 2.5 microg/ml for 24, 48 and 72 h.
The CB 2'-ph had an inhibitory effect on all tested types of cell proliferation but only HUVEC and BAEC proliferation was specifically inhibited in a dose-dependent manner. In addition, CB 2'-ph inhibited VEGF- or bFGF-induced proliferation and migration of HUVECs in a dose-dependent manner.
These results indicate that CB 2'-ph, a farnesyl transferase inhibitor is thought to be an effective inhibitor of vascular endothelial cell proliferation and migration.
评估法尼基转移酶抑制剂2'-O-苯甲酰肉桂醛(CB 2'-ph)对血管内皮细胞增殖和迁移的抑制作用。
用CB 2'-ph处理牛晶状体上皮细胞、牛角膜内皮细胞、牛角膜细胞、牛主动脉内皮细胞(BAECs)和人脐静脉内皮细胞(HUVECs),以确定其细胞类型特异性和抗增殖作用。为了抑制血管内皮生长因子(VEGF)或碱性成纤维细胞生长因子(bFGF)诱导的HUVECs增殖,用不同浓度的CB 2'-ph处理这些细胞。采用MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四氮唑)法评估增殖情况。还进行了迁移试验以确定CB 2'-ph对HUVECs的影响。在用浓度为0、1.5和2.5微克/毫升的CB 2'-ph处理单层细胞24、48和72小时后,测量HUVECs从刮擦边缘向外生长的距离。
CB 2'-ph对所有测试的细胞增殖类型均有抑制作用,但仅对HUVEC和BAEC的增殖有特异性的剂量依赖性抑制作用。此外,CB 2'-ph以剂量依赖性方式抑制VEGF或bFGF诱导的HUVECs增殖和迁移。
这些结果表明,法尼基转移酶抑制剂CB 2'-ph被认为是血管内皮细胞增殖和迁移的有效抑制剂。