IFNα在人骨髓瘤细胞系Sko-007中的生物学效应及分子机制  

Study on the biological activity and molecular mechanism of IFNα on human myeloma cell line Sko-007

作　　者：宋伦[1] 黎燕[1] 孙英勋[1] 沈倍奋[1] 

机构地区：[1]军事医学科学院基础医学研究所,北京100850

出　　处：《中华血液学杂志》2002年第10期517-519,共3页Chinese Journal of Hematology

基　　金：国家杰出青年科学基金资助项目 ( 3992 5 0 19)

摘　　要：目的　研究IFNα在人骨髓瘤细胞系Sko 0 0 7中的生物学效应及分子机制。方法　MTT方法检测IFNα对Sko 0 0 7细胞生长的影响 ;流式细胞术检测IFNα作用后Sko 0 0 7细胞生长周期及其表面IL 6受体 (IL 6R)α链和 β链 (gp130 )表达水平的改变 ;免疫印迹法检测能够介导细胞生长的Ras MAPK途径中蛋白激酶ERK在IFNα刺激作用下的活化以及Bcl 2家族抗凋亡蛋白———Bcl 2 ,Bcl xL 和Mcl 1在IFNα刺激前、后的表达改变。结果　IFNα能够抑制Sko 0 0 7细胞周期行进 ,使处于G0 G1 期的细胞数明显增加 (从 41.1%增至 84.1% ) ,而S期细胞比例显著下降 (从 5 7.1%降至 13.3% ) ;同时IFNα可表现出细胞增殖抑制效应 ,最大抑制率为 88%。IFNα刺激后 ,Sko 0 0 7细胞表面gp130表达明显下调 ;同时蛋白激酶ERK活化受抑 ;Bcl 2降解 ;Bcl xL 表达下降。结论　IFNα可通过下调细胞表面gp130表达、抑制蛋白激酶ERK活化和促进Bcl 2家族抗凋亡蛋白降解而实现其对Sko 0 0Objective To investigate the biological activity and molecular mechanism of interferon α(IFNα) on human myeloma cell line Sko-007.Methods The effect of IFNα on the growth of Sko-007 cells was measured by MTT assay.Cells cycle distribution and the expression of two IL-6 receptor chains (IL-6R and gp130) on Sko-007 cell surface in the absence or presence of IFNα were monitored by FACS analysis. The activation state of protein kinase ERK, which is involved in Ras/MAPK signal transduction pathway mediating cell survival and proliferation, and the expression of anti-apoptotic Bcl-2 family proteins--Bcl-2, Bcl-x L and Mcl-1 in Sko-007 cells with or without IFNα were determined by immunoblot assay. Result IFNα arrested Sko-007 cell cycle progression. After stimulation with IFNα, an obvious increase in G 0/G 1 phase (41.1%→84.1%) and decrease in S phase (57.1%→13 3%) of Sko-007 cell cycle distribution can be observed. Moreover, the proliferation of Sko-007 cells was dramatically inhibited in the presence of IFNα, with a maximal inhibitory rate up to 88%. In addition, the expression of gp130 on cell surface, the activation of protein kinase ERK and the expression of Bcl-2 and Bcl-x L were all down-regualted in IFNα-stimulated Sko-007 cells.Conclusion The inhibitory effect of IFNα on the proliferation of Sko-007 cells was mediated by gp130 down-regulation, degradation of Bcl-2 family anti-apoptotic proteins and inhibition of ERK activation.

关 键 词：干扰素Α 多发性骨髓瘤 增殖抑制 蛋白激酶ERK BCL-2蛋白 

分 类 号：R733.3[医药卫生—肿瘤]