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部分乙酰化壳寡糖对肿瘤血管微系统的肝癌细胞转移抑制作用。

Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem.

机构信息

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Mar Drugs. 2019 Jul 13;17(7):415. doi: 10.3390/md17070415.

Abstract

Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage(s) of tumor metastasis COS targeted. To study the inhibitory effects of a new partially acetylated chitooligosaccharide (paCOS) with fraction of acetylation (F) 0.46 on each phase of liver cancer cell metastasis, a dynamic tumor-vessel microsystem undergoing physiological flow was leveraged. paCOS (F = 0.46) significantly inhibited proliferation of HepG2 cells through vascular absorption on the chip, and inhibited migration of HepG2 cells by inhibiting the formation of pseudopod in liver tumor cells. It was also found that paCOS at 10 μg/mL had a stronger inhibitory effect on liver tumor cells invading blood vessels than that of paCOS at 100 μg/mL, and paCOS at 100 μg/mL, which had a significant destructive effect on tumor vascular growth and barrier function. Moreover, paCOS reduced the number of liver tumor cells adhering onto the surface of HUVECs layer after 3 h of treatment. Therefore, the results revealed that paCOS had considerable potential as drugs for anti-tumor metastasis.

摘要

壳寡糖(COS)是自然界中唯一带正电荷的寡糖,具有抗肿瘤活性。然而,COS 对肿瘤转移不同阶段的抑制作用尚不清楚,也不清楚 COS 针对肿瘤转移的哪个(些)阶段。为了研究乙酰化度为 0.46 的新型部分乙酰化壳寡糖(paCOS)在肝癌细胞转移的各个阶段的抑制作用,利用了在生理流动下的动态肿瘤血管微系统。paCOS(F=0.46)通过芯片上的血管吸收显著抑制 HepG2 细胞的增殖,并通过抑制肝肿瘤细胞伪足的形成抑制 HepG2 细胞的迁移。还发现,10μg/mL 的 paCOS 对侵犯血管的肝癌细胞的抑制作用强于 100μg/mL 的 paCOS,而 100μg/mL 的 paCOS 对肿瘤血管生长和屏障功能具有显著的破坏作用。此外,paCOS 减少了处理 3 小时后附着在 HUVEC 层表面的肝癌细胞数量。因此,结果表明 paCOS 具有作为抗肿瘤转移药物的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cb1/6669685/4a65d9494415/marinedrugs-17-00415-g001.jpg

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