5-羟基川陈皮素对肿瘤细胞糖胺聚糖含量和结构的影响

发布时间：2018-04-26 01:06

本文选题：糖胺聚糖 + -羟基川陈皮素　；参考：《中国海洋大学学报(自然科学版)》2017年04期

【摘要】：糖胺聚糖(GAGs)位于细胞膜及胞外基质,它通过与多种生长因子受体结合来介导细胞内的信号转导,进而调控细胞的增殖与分化。研究表明,GAGs结构或含量变化在肿瘤发生和发展中发挥了重要作用。黄酮类化合物可影响肿瘤细胞表面GAGs合成,前期研究发现,5-羟基川陈皮素(5HPMF)可通过干预细胞内多种信号通路进而抑制肺癌和结肠癌细胞增殖,然而,5HPMF如何影响GAGs结构和含量的变化进而介导信号转导通路的机制还不清楚。基于此,本研究利用BaF3细胞模型,流式细胞仪及HPLC技术,首次探讨了5HPMF对肺癌和结肠癌细胞GAGs含量和结构的影响。结果表明,来源于HT29和A549细胞的GAGs可增强FGF1介导的BaF3细胞生长而5HPMF(10μmol·L-1)则显著地抑制其生长作用,且5HPMF可显著地降低HCT116和A549细胞表面FGF2或FGF8介导的GAGs·FGF·FGFR三元复合物的荧光强度,但是5HPMF对GAGs中葡萄糖胺和半乳糖胺的含量及两者比例无明显影响,由此可推断5HPMF可能通过影响肺癌和结肠癌细胞表面GAGs结构而介导细胞内部信号转导。本研究为进一步探讨5HPMF对肺癌和结肠癌细胞表面GAGs二糖结构的变化与活性之间的相关性奠定了实验基础。
[Abstract]:Glycosaminoglycan (GAGs) is located on the cell membrane and extracellular matrix. It mediates intracellular signal transduction by binding with multiple growth factor receptors and then regulates cell proliferation and differentiation. Studies have shown that changes in structure or content of gags play an important role in tumorigenesis and development. Flavonoids can affect the synthesis of GAGs on the surface of tumor cells. It has been found in previous studies that 5HPMF can inhibit the proliferation of lung and colon cancer cells by interfering with many signaling pathways. However, it is not clear how 5 HPMF affects the changes of GAGs structure and content and thus mediates the signal transduction pathway. Based on this, the effects of 5HPMF on the content and structure of GAGs in lung and colon cancer cells were investigated for the first time by using BaF3 cell model, flow cytometry and HPLC technique. The results showed that GAGs derived from HT29 and A549 cells could enhance the growth of BaF3 cells mediated by FGF1, while 5HPMF(10 渭 mol L -1 could significantly inhibit the growth of BaF3 cells, and 5HPMF could significantly reduce the fluorescence intensity of FGF2 or FGF8 mediated GAGs FGF FGFR ternary complexes on the surface of HCT116 and A549 cells. However, 5HPMF had no significant effect on the content and ratio of glucosamine and galactosamine in GAGs. It is concluded that 5HPMF may mediate intracellular signal transduction by affecting the surface GAGs structure of lung and colon cancer cells. This study provides an experimental basis for the further study of the relationship between the changes of GAGs disaccharide structure and the activity of 5HPMF on the surface of lung and colon cancer cells.
【作者单位】：中国海洋大学医药学院海洋药物教育部重点实验室;中国海洋大学山东省糖科学与糖工程重点实验室;
【基金】：教育部新教师基金项目(20130132120006) 山东省科技发展计划项目(2012GSF11912&2014GGH215001)资助~~
【分类号】：R730.5

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