Huang Lulin, Zeng Hui, Jin Can, Ma Xiaonan, Zhang Yiwen, Huang Chunfan, Du Zhenyun, Ding Kan
Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China.
Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province 210029, China.
Carbohydr Polym. 2022 Aug 1;289:119412. doi: 10.1016/j.carbpol.2022.119412. Epub 2022 Mar 28.
Evidences propound tumor growth may be impeded by blocking angiogenesis. Before we showed that sulfated glucan or arabinogalactan might bind to BMP2 or its receptors to inhibit angiogenesis. Whether sulfated galactoglucan can target both BMPRIA and BMPRII to impede angiogenesis and tumor cells growth is still vague. Here, we prepare galactoglucan and its sulfated derivatives Sul-CDA-0.05. The sulfate groups substituted are at the C-6 of 1, 4-linked α-Glcp and 1, 4-linked α-Galp backbone and at the C-6 of branch chain T-linked α-Glcp. Sul-CDA-0.05 can inhibit angiogenesis in vitro and in vivo. Indeed, Sul-CDA-0.05 impedes xenografted A549 lung tumor cells growth. Mechanism study demonstrates that this polysaccharide may target both BMPRIA and BMPRII to block BMP/Smad/Id1 signaling and attenuate VEGF and its transcription factor. Our evidences suggest that Sul-CDA-0.05 may be a new drug candidate for anti-lung cancer therapy by targeting both BMPRIA and BMPRII.
有证据表明,阻断血管生成可能会抑制肿瘤生长。此前我们发现硫酸化葡聚糖或阿拉伯半乳聚糖可能与骨形态发生蛋白2(BMP2)或其受体结合以抑制血管生成。硫酸化半乳葡聚糖是否能靶向骨形态发生蛋白受体1A(BMPRIA)和骨形态发生蛋白受体2(BMPRII)以阻碍血管生成和肿瘤细胞生长仍不明确。在此,我们制备了半乳葡聚糖及其硫酸化衍生物Sul-CDA-0.05。被取代的硫酸基团位于1,4-连接的α-葡萄糖(Glcp)和1,4-连接的α-半乳糖(Galp)主链的C-6位以及支链T-连接的α-葡萄糖的C-6位。Sul-CDA-0.05在体外和体内均可抑制血管生成。实际上,Sul-CDA-0.05可阻碍异种移植的A549肺癌细胞生长。机制研究表明,这种多糖可能靶向BMPRIA和BMPRII,以阻断BMP/Smad/Id1信号传导并减弱血管内皮生长因子(VEGF)及其转录因子。我们的证据表明,Sul-CDA-0.05可能是一种通过靶向BMPRIA和BMPRII用于抗肺癌治疗的新型候选药物。