神经调节蛋白-1对人脑胶质瘤细胞侵袭与迁移能力的影响  

Effect of neuregulin-1 on invasion and migration ability of human glioma cells

作　　者：彭康[1] 胡金霞[2] 石琼[2] 郭堂军 解哨 周秀萍[2] 于如同[2] 

机构地区：[1]徐州医学院研究生学院,221002 [2]徐州医学院神经系统疾病研究所,221002

出　　处：《中华神经外科杂志》2015年第4期397-401,共5页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金（81272777,81302175,No.81472345）;江苏省高校自然科学基金（13KJB320025）.

摘　　要：目的 了解神经调节蛋白-1（neuregulin-1,NRG-1）与脑胶质瘤发生发展的相关性以及NRG-1对脑胶质瘤细胞侵袭与迁移能力的影响.方法 采用免疫印迹法检测NRG-1蛋白在非瘤脑组织与各级别胶质瘤组织标本中表达情况.采用细胞划痕实验观察下调NRG-1后U251细胞迁移能力的变化;Transwell侵袭实验观察细胞侵袭能力的变化;明胶酶谱法分析下调NRG-1后基质金属酶2（MMP2）分泌的变化.结果 NRG-1在脑胶质瘤组织中的表达水平（1.17±0.13）明显高于非瘤脑组织（0.59±0.12） （P ＜0.01）;与对照组相比,下调NRG-1后,细胞迁移能力降低,NRG-1-si834组和NRG-1-si868组穿过Matrigel基质胶及滤膜的细胞数明显减少,分别为对照组的55％和47％;同时MMP2的分泌明显降低,分别为（44.51 ±2.72）％和（38.31 ±3.46）％,差异有统计学意义（P＜0.01）.结论 脑胶质瘤中NRG-1蛋白表达水平升高.下调NRG-1可以抑制胶质瘤细胞的侵袭和迁移能力并抑制MMP2的分泌。Objective To study the relationship between the protein level of Neuregulin-1 （NRG-1） and glioma progression and the effect of NRG-1 on the invasive and migratory ability of glioma cells.Methods The protein expression level of NRG-1 was detected by Western blot （WB） in nontumorous brain tissues and glioma specimens.Next,the effect of NRG-1 down-regulation on the migratory and invasive ability of glioma cells were examined by wound healing assay and matrigel-precoated transwell chambers,respectively.Last,the excretion of MMP2 was examined by gelatin zymography assay after down-regulating the NRG-1.Results The protein level of NRG-1 in human gliomas was considerably higher than that of nontumorous brain tissues.Compared with the control group,the number of cells acrossing the wound edge decreased in NRG-1 down-regulation group （P 〈 0.01）.In the matrigel invasion assay,cell number invading through matrigel dramatically decreased in NRG-1-siRNA transfection group （P 〈 0.01）.Gelatin zymography revealed that the excretion of MMP2 of NRG-1 down-regulation group was obviously lower than that of the control group （P 〈 0.01）.Conclusions The expression level of NRG-1 in human gliomas was higher than that in nontumorous brain tissues,indicating the involvement of NRG-1 in glioma development.Down-regulation of NRG-1 inhibited glioma cell invasion and migration and the excretion of MMP2 in vitro.

关 键 词：神经胶质瘤 神经调节蛋白-1 细胞迁移 肿瘤侵袭 基质金属酶2 

分 类 号：R739.4[医药卫生—肿瘤]