【摘要】 目的:探讨褐藻糖胶对多发性骨髓瘤U266细胞的影响及可能的作用机制。方法:采用不同浓度的褐藻糖胶(10、25和50μg/mL)处理U266细胞24、48及72 h后,细胞计数试剂盒-8(cell counting kit-8,CCK-8)检测其对细胞的增殖抑制率;FCM法检测细胞的凋亡率;蛋白质印迹法分别检测大鼠肉瘤基因(rat sarcoma,RAS)、p38、磷酸化-p38(phospho-p38,p-p38)、sonic Hedgehog(Shh)和胶质瘤相关基因同系物1(glioma-associated oncogene homolog 1,GLI1)蛋白的表达水平。结果:不同浓度的褐藻糖胶(10、25和50μg/mL)对U266细胞的增殖抑制作用仅呈浓度依赖性增强;U266细胞经不同浓度的褐藻糖胶(10、25和50μg/mL)处理24 h后,其凋亡率分别为(6.73±2.30)%、(9.12±1.90)%和(20.13±2.10)%,均高于对照组的(4.08±1.60)%(P<0.05);蛋白质印迹法检测结果显示,Ras、p-p38、Shh和GLI1蛋白的表达明显低于对照组(P<0.05)。结论:褐藻糖胶可通过介导Ras-p38MAPK和Shh-GLI1信号通路的活化,抑制U266细胞增殖,并诱导细胞凋亡。更多还原

【Abstract】 Objective:To investigate the effect of fucoidan on multiple myeloma U266 cells and its possible molecular mechanism.Methods:The multiple myeloma U266 cells were treated with 10,25 and 50 μg/mL fucoidan for 24,48 and 72 h,respectively.The growth inhibitory rate of U266 cells was determined by cell counting kit-8(CCK-8) assay.The apoptosis rate was measured by flow cytometry.The expression levels of RAS,p38,phospho-p38,sonic Hedgehog(Shh) and glioma-associated oncogene homolog 1(GLI1) were detected by Western blotting.Results:The growth of multiple myeloma U266 cells treated with different concentrations of fucoidan(10,25 and 50 μg/mL) was inhibited only in a dosedependent manner.The apoptosis rates of U266 cells treated with 10,25 and 50 μg/mL fucoidan for 24h were(6.73±2.30)%,(9.12±1.90)% and(20.13±2.10)%,respectively,which were higher than that of the U266 cells without fucoidan intervention [control:(4.08±1.60)%; P<0.05).The expression levels of RAS,phospho-p38,Shh and GLI1 proteins in U266 cells treated with fucoidan were significantly lower than that of the control(P<0.05).Conclusion:Fucoidan inhibits proliferation and induces apoptosis of U266 cells by inhibiting Ras-p38MAPK and Shh-GLI1 signaling pathways.更多还原