| 张卫彬,范晨晨,蒋昊.双重糖链编辑对EGFR信号转导调控的研究[J].中国海洋药物,2025,(2):-. |
| 双重糖链编辑对EGFR信号转导调控的研究 |
| Study on the method for in situ dual glycan editing and its modulation on EGFR signaling |
| 投稿时间：2023-04-25 修订日期：2023-05-10 |
| DOI： |
| 中文关键词: 表皮生长因子受体(EGFR) 双重糖链原位编辑(ISGE) 岩藻糖 唾液酸 肺癌细胞 |
| English Keywords:Epidermal Growth Factor Receptor (EGFR) In Situ Dual Glycan Editing (ISGE) Sialic acid Fucose Lung cancer cell |
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| 中文摘要: |
| 目的 开发并建立一种细胞表面双重糖链编辑的方法,研究不同组合唾液酸和岩藻糖类似物对肺癌细胞EGFR信号通路的影响,筛选对EGFR信号通路具有显著抑制作用的糖链编辑方案。方法 利用化学酶法合成2种CMP-Sia类似物和6种GDP-Fucose类似物作为糖链原位编辑(ISGE)的糖供体；利用流式细胞术对双重糖链编辑方法的可行性进行验证；利用Western Blot筛选出对 EGFR信号有明显抑制效果的 ISGE方案；利用细胞划痕实验验证筛选出的组合对细胞迁移的抑制作用。 结果 成功制备了2种CMP-Sia类似物和6种GDP-Fucose类似物,确定了双重糖链编辑的最佳反应时间以及反应顺序,并筛选出SiaAz+FucOMe组合为最佳的ISGE方案。结论 基于双重糖链编辑的方法对EGFR进行唾液酸化与岩藻糖化可以显著抑制其信号通路的转导,为海洋岩藻多糖抗肿瘤机制研究提供了新的思路。 |
| English Summary: |
| Objective. To develop and establish a strategy for cell surface dual glycan editing ,and explore the effects of different combinations of sialic acid and fucose analogues on EGFR signaling pathways in lung cancer cells, and to screen out the glycan editing strategies with significant inhibition of EGFR signaling pathway. Methods. Two CMP-Sia analogues and six GDP-Fucose analogues were synthesized by chemical enzymatic method as glycosyl donors for in situ glycan editing (ISGE). Flow cytometry was used to verify the feasibility of in situ dual glycan editing. Western Blot was used to screen out the dual glycan editing strategies with obvious inhibition on EGFR. Cell scratch assay was used to verify the inhibitory effect of the selected combinations on cell migration. Results. Two CMP-Sia analogues and six GDP-Fucose analogues were successfully synthesized. The optimal reaction time and sequence of dual glycan editing were determined, and SiaAz+FucOMe was selected as the best ISGE strategy. Conclusion. The sialylation and fucosylation of EGFR based on dual glycan editing can significantly inhibit the transduction of its signaling pathway, which provides a new idea for the study of anti-tumor mechanism of marine fucoidan. |
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