褐藻糖胶通过抑制Ras-p38MAPK和Shh-GLI1信号通路诱导多发性骨髓瘤细胞的凋亡  

Fucoidan induces apoptosis of multiple myeloma cells by inhibiting Ras-p38MAPK and Shh-GLI1 signaling pathways

作　　者：吕敬龙[1] 肖青[1] 刘欣[1] 王利[1] 王欣[1] 杨泽松[1] 张红宾[1] 董浦江[2] 

机构地区：[1]重庆医科大学附属第一医院血液科,重庆400016 [2]重庆医科大学神经病学国家重点实验室,重庆400016

出　　处：《肿瘤》2013年第11期991-995,共5页Tumor

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。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 dose-dependent manner. The apoptosis rates of U266 cells treated with 10, 25 and 50 μg/mL fucoidan for 24 h 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.

关 键 词：多发性骨髓瘤 海带属 褐藻糖胶 丝裂原激活蛋白激酶信号系统 HEDGEHOG信号通路 

分 类 号：R733.3[医药卫生—肿瘤]