组成性JNK活化促进B淋巴瘤细胞增殖  

Hyperactivation of c-Jun NH_2-terminal Protein Kinase Contributes to the Proliferation of B lymphoma Cells

作　　者：郭媛媛[1,2] 崔健[1] 侯春梅[1] 王庆阳[1] 王晶[1] 马远方[2] 张纪岩[1] 

机构地区：[1]军事医学科学院基础医学研究所分子免疫学实验室,北京100850 [2]河南大学医学院免疫学研究所,河南开封475001

出　　处：《中国实验血液学杂志》2011年第1期100-104,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金项目(编号30973547);973项目(编号2010CB911904)

摘　　要：本研究以人B淋巴瘤细胞系Daudi和Raji为研究对象,探讨组成性JNK活化对B淋巴瘤细胞增殖的影响。用Western blot检测Daudi、Raji B淋巴瘤细胞中组成性JNK的变化;用免疫荧光方法检测Daudi、raji B淋巴瘤细胞中JNK的亚细胞定位;用JNK抑制因子(SP600125)处理Daudi和raji B淋巴瘤细胞,用流式细胞术检测其细胞周期;用ATPLite法检测SP600125对Daudi、Raji B淋巴瘤细胞生长的影响。结果显示:Daudi和raji B淋巴瘤细胞有组成性JNK活化;Daudi和raji B淋巴瘤细胞JNK亚细胞定位异常,存在不同程度的入核;JNK特异性抑制因子SP600125诱导B淋巴瘤细胞Daudi、Raji G2/M期细胞比例升高,并具有时间依赖性,且G0/G1峰前出现亚二倍体峰,证实SP600125在B淋巴瘤细胞中诱导G2/M阻滞和凋亡。ATPLite检测结果显示,SP600125显著抑制Daudi和Raji B淋巴瘤细胞的生长,并随着抑制因子浓度的升高,抑制作用更加明显,呈现剂量依赖性。结论:组成性JNK活化促进Daudi和Raji B淋巴瘤细胞增殖。JNK活性的升高通过促进JNK从胞浆进入胞核来促进B淋巴瘤细胞的增殖。SP600125通过多种机制阻抑JNK的活性抑制B淋巴瘤细胞的恶性生长。JNK可作为临床治疗B淋巴瘤的潜在靶点。This study was purposed to explore the effect of hyperactivation of c-Jun NH2-terminal protein kinase（JNK） on the proliferation of B lymphoma cells.The human B lymphoma cell lines Daudi and Raji were chosen as research objects.The expression of JNK protein was determined by Western blot.The subcellular localization of JNK protein was detected by immunofluorescence.The cell cycle was analyzed by flow cytmetry.The suppressive effect of JNK inhibitor SP600125 on the proliferation of Daudi and Raji cells was assayed by ATPLite method.The results demonstrated that hyperactivation of JNK has been found in Daudi and Raji cells.Immunofluorescence confirmed the aberrant subcellular localization of JNK protein in Daudi and Raji cells.Cell cycle assay revealed that Daudi and Raji cells underwent G2-M arrest in the presence of SP600125.Furthermore,Daudi and Raji cells showed significant increase in sub-G1 population,an indicator of apoptotic cells,with the treatment of JNK inhibitors.These data suggested that JNK inhibitors suppressed the growth of B lymphoma cells via cell cycle arrest and apoptosis.Daudi and Raji cells treated with different concentrations of JNK selective inhibitor SP600125 showed dose-dependent reduction in the growth of Daudi and Raji cells.It is concluded that hyperactivation of JNK enhance the proliferation of Daudi and Raji cells.The aberrant subcellualr localization of JNK protein may facilitate the nuclear accumulation of basal JNK activity,which made JNK to be a potential target to treat human B lymphoma.

关 键 词：JNK B淋巴瘤细胞 DAUDI细胞 RAJI细胞 亚细胞定位 

分 类 号：R733.1[医药卫生—肿瘤]