Cheng Jing-Jy, Huang Nai-Kuei, Chang Tun-Tschu, Wang Danny Ling, Lu Mei-Kuang
National Research Institute of Chinese Medicine, Room 739, No155-1, Section 2, Li-Nung Street, Pei-tou District (112), Taipei, Taiwan.
Life Sci. 2005 May 13;76(26):3029-42. doi: 10.1016/j.lfs.2004.11.023.
The main purposes of this study were to investigate the regulation of polysaccharides isolated from A. cinnamomea on vascular endothelial growth factor (VEGF)-induced cyclin D1 expression and down stream signaling pathway that may correlate with their anti-angiogenc effects in endothelial cells (ECs). Crude and fractionated polysaccharides (Fra-1 to Fra-4) of A. cinnamomea showed slightly toxicity to ECs as compared with their inhibition concentration on angiogenic-related gene expression. The crude extract and fractionated fractions, except for Fra-2, of A. cinnamomea polysaccharides significantly decreased VEGFR2 phosphorylation on tyrosine 1054/1059, cyclin D1 promotor activity, and protein expression induced by VEGF. Crude extract of A. cinnamomea polysaccharides inhibited the binding of VEGF to KDR/flk-1 in a dose-dependent manner. These results indicated that inhibition of VEGF interaction with VEGF receptor 2 is the mechanism serves A. cinnamomea as a protective mechanism composing the anti-angiogenesis function. Furthermore, A. cinnamomea polysaccharides also blocked VEGF-induced migration and capillary-like tube formation of ECs on Matrigel. Taken together, these results indicate that A. cinnamomea polysaccharides inhibit cyclin D1 expression through inhibition of VEGF receptor signaling, leading to the suppression of angiogenesis.
本研究的主要目的是探讨从肉桂中分离出的多糖对血管内皮生长因子（VEGF）诱导的细胞周期蛋白D1表达的调节作用，以及可能与其在内皮细胞（ECs）中的抗血管生成作用相关的下游信号通路。与它们对血管生成相关基因表达的抑制浓度相比，肉桂粗多糖和分级多糖（Fra-1至Fra-4）对ECs显示出轻微的毒性。肉桂多糖的粗提物和分级组分（Fra-2除外）显著降低了VEGFR2在酪氨酸1054/1059处的磷酸化、细胞周期蛋白D1启动子活性以及VEGF诱导的蛋白表达。肉桂多糖粗提物以剂量依赖性方式抑制VEGF与KDR/flk-1的结合。这些结果表明，抑制VEGF与VEGF受体2的相互作用是肉桂发挥抗血管生成功能的保护机制。此外，肉桂多糖还阻断了VEGF诱导的ECs在基质胶上的迁移和毛细血管样管形成。综上所述，这些结果表明肉桂多糖通过抑制VEGF受体信号传导来抑制细胞周期蛋白D1的表达，从而导致血管生成的抑制。
