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硫酸软骨素-硒纳米颗粒通过调节VEGFR2介导的PI3K/Akt信号通路抑制血管生成。

Selenium-Chondroitin Sulfate Nanoparticles Inhibit Angiogenesis by Regulating the VEGFR2-Mediated PI3K/Akt Pathway.

作者信息

Zheng Xia, Liu Xiaofei, Wang Zhuo, Li Rui, Zhao Qiaoli, Song Bingbing, Cheong Kit-Leong, Chen Jianping, Zhong Saiyi

机构信息

College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.

Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China.

出版信息

Mar Drugs. 2025 Jan 2;23(1):22. doi: 10.3390/md23010022.

DOI:10.3390/md23010022
PMID:39852524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11766607/
Abstract

Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (NaSeO) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor.

摘要

硫酸软骨素(CS)是一类共价连接到蛋白质上形成蛋白聚糖的糖胺聚糖,广泛分布于动物组织的细胞外基质和细胞表面。在我们之前的研究中,通过抗坏血酸(Vc)和亚硒酸钠(NaSeO)的氧化还原反应,将CS用作合成硒代硫酸软骨素(SeCS)的模板,并且我们发现SeCS可以抑制肿瘤细胞的增殖和侵袭。然而,其对血管生成的影响及其潜在机制尚不清楚。在本研究中,基于对人脐静脉内皮细胞(HUVECs)管形成和迁移的抑制,我们分析了SeCS对体外管形成的影响,并使用鸡胚绒毛尿囊膜(CAM)试验评估了SeCS的体内血管生成作用。结果表明,SeCS显著抑制鸡胚尿囊膜的血管生成。进一步的机制分析表明,SeCS对VEGFR2表达及其下游PI3K/Akt信号通路具有强烈的抑制作用,这促成了其抗血管生成作用。总之,SeCS在HUVEC细胞模型和CAM模型中显示出良好的抗血管生成作用,表明它可能是一种潜在的血管生成抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/47bba4b7545c/marinedrugs-23-00022-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/f825cf0f18bf/marinedrugs-23-00022-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/c62f541f1970/marinedrugs-23-00022-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/217d18d6e721/marinedrugs-23-00022-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/75d569499dc3/marinedrugs-23-00022-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/e2d960c2ec6c/marinedrugs-23-00022-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/8a09cc47573c/marinedrugs-23-00022-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/05e473bca4a2/marinedrugs-23-00022-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/307feb5836c9/marinedrugs-23-00022-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/47bba4b7545c/marinedrugs-23-00022-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/f825cf0f18bf/marinedrugs-23-00022-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/c62f541f1970/marinedrugs-23-00022-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/217d18d6e721/marinedrugs-23-00022-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/75d569499dc3/marinedrugs-23-00022-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/e2d960c2ec6c/marinedrugs-23-00022-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/8a09cc47573c/marinedrugs-23-00022-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/05e473bca4a2/marinedrugs-23-00022-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/307feb5836c9/marinedrugs-23-00022-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f8/11766607/47bba4b7545c/marinedrugs-23-00022-g009.jpg

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