State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Carbohydr Polym. 2015 May 5;121:328-35. doi: 10.1016/j.carbpol.2014.11.073. Epub 2015 Jan 2.
Angiogenesis plays an essential role in tumor development. Blocking angiogenesis in tumor has become a promising tactic in limiting cancer progression. Here, an arabinogalactan polysaccharide, RN1 was isolated from flowers of Panax notoginseng. Its structure was determined to possess a backbone of 1,6-linked Galp branched at C3 by side 1,3-linked Galp, with branches attached at position O-3 of it. The branches mainly contained 1,5-linked, 1,3,5-linked, terminal Arabinose and terminal Galactose. RN1 could inhibit microvessel formation in the BxPC-3 pancreatic cancer cell xenograft tumor in nude mice. The antiangiogenesis assay showed that RN1 could reduce the migratory activity of endothelial cells and their ability of tube formation on matrigel, but no effect on endothelial cells growth. Further studies revealed that RN1 could inhibit BMP2/Smad1/5/8/Id1 signaling. All those data indicated the RN1 had an antiangiogenic effect via BMP2 signaling and could be a potential novel inhibitor of angiogenesis.
血管生成在肿瘤发展中起着至关重要的作用。阻断肿瘤中的血管生成已成为限制癌症进展的一种有前途的策略。在这里，从三七花中分离得到一种阿拉伯半乳聚糖多糖 RN1。其结构确定为具有由 C3 上的侧 1,3-连接的 Galp 分支的 1,6-连接的 Galp 主链，分支附着在其上的 O-3 位置。该分支主要含有 1,5-连接、1,3,5-连接、末端阿拉伯糖和末端半乳糖。RN1 可抑制裸鼠 BxPC-3 胰腺癌细胞异种移植肿瘤中的微血管形成。血管生成抑制试验表明，RN1 可降低内皮细胞的迁移活性及其在基质胶上形成管的能力，但对内皮细胞生长没有影响。进一步的研究表明，RN1 可以抑制 BMP2/Smad1/5/8/Id1 信号通路。所有这些数据表明，RN1 通过 BMP2 信号具有抗血管生成作用，可能是一种新型的血管生成抑制剂。
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