趋化因子受体4拮抗多肽对Ⅰ型神经纤维瘤病细胞增殖与迁移的抑制作用OA

Objective The purpose is to screen antagonistic polypeptides of chemokine receptor 4(CXCR4)that have a strong binding effect on Neurofibromatosis type 1(NF1)cells,and to study their anti-proliferation and migration abilities on human normal Schwann cells and NF1 cells,and to reveal their underlying mecha-nisms.Methods The cell line WZJ derived from NF1 patients were taken as the research objects.The expression of CXCR4 receptor in the cells and the binding of polypeptides to the cells were detected by flow cytometry;Cell proliferation was determined by CCK8;The migration of cells was observed by transwell assay;The changes in p-Erk levels were detected by Western blot.Results The results showed that the CXCR4 receptor was highly ex-pressed in NF1-related WZJ cells,and the antagonistic polypeptide E5 targeting CXCR4 could specifically bind to WZJ cells.The anti-cell proliferation ability of E5 is cell-selective and has a significant inhibitory effect on the proliferation of cells with high expression of CXCR4.E5 could significantly inhibit the migration of NF1 cells chemotactic by CXCL12.Mechanism studies have shown that E5 inhibits the response of WZJ cells to CXCL12 stimulation by suppressing the expression of p-Erk.Conclusion The study discovered a polypeptide that could ef-fectively bind to NF1 cells with high expression of CXCR4 receptor.It could inhibit the proliferation and migra-tion of NF1 cells by down-regulating the phosphorylation of Erk activated by CXCL12 and has translational appli-cation potential in the treatment of NF1.