NF-κB p65对人非霍奇金淋巴瘤细胞凋亡调控的研究  

Modulation of cancer cell apoptosis by NF-κB p65 in human non-Hodgkin lymphoma

作　　者：乔俏[1] 姜元军[2] 李光[1] 

机构地区：[1]中国医科大学附属第一医院放疗科,辽宁沈阳110001 [2]中国医科大学附属第一医院泌尿外科,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2013年第14期1079-1082,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：辽宁省教育厅基金(2009A754)

摘　　要：目的:研究NF-κB p65对人非霍奇金淋巴瘤(NHL)细胞凋亡的作用及其调控机制。方法:以NF-κB p65抑制剂quinazoline(QNZ)处理人NHL细胞,采用Annexin-Ⅴ染色方法检测肿瘤凋亡水平的变化,蛋白质印迹法检测各细胞系中Survivin蛋白及凋亡相关蛋白Bax、Bcl-2和Cleaved Caspase-3的表达水平;进一步应用实时定量PCR方法检测Survivin mRNA水平。结果:NF-κB p65抑制剂QNZ能够诱导NHL细胞的凋亡(P<0.05),具有时间-剂量依赖性。10nmol/L QNZ作用72h后Namalwa、Ramos和Raji细胞凋亡率分别为(13.5±2.7)%、(16.4±2.8)%和(15.8±2.5)%。抑制NF-κB p65的表达能够显著下调淋巴瘤细胞中Survivin蛋白的表达水平,10nmol/L QNZ作用72h后Namalwa、Ramos和Raji细胞中Survivin蛋白表达为0.58±0.06、0.54±0.03和0.51±0.09。同时,凋亡相关蛋白Bcl-2表达减低而Bax和Cleaved Caspase-3蛋白表达增加,Bcl-2与Bax蛋白比值明显降低,与对照组相比差异均有统计学意义,P<0.05。预处理QNZ后3种NHL细胞Survivin mRNA均不同程度下降,随浓度增加其作用更为明显,P<0.05。结论:抑制NF-κB p65能够诱导NHL细胞凋亡,其机制可能与下调Survivin蛋白表达水平及对凋亡相关蛋白Bcl-2家族的调节有关。OBJECTIVE： To investigate the role of NF-kB in control of apoptosis in human non-Hodgkin lymphoma （NHL） cells and to explore the mechanism mediating this effect. METHODS： Three human NHL cell lines,Namalwa, Ramos, Raji cells were treated with QNZ,a specific NF-kB antagonist. Apoptosis levels were determined with Annexin V dying method. Expression levels of Survivin and apoptotic related protein Bax, Bcl-2 and cleaved Caspase-3 were evaluated by Western blot. Survivin mRNA expression was determined by real-time PCR. RESULTS： Inhibition of NF kB with QNZ induced apoptosis in all three human NHL eel1 lines was in a time and dose dependent manner （P〈0.05）. After incubated with 10nmol/L QNZ for 72 h,apoptosis rates of Namalwa,Ramos, Raji cells were （13.5±2.7）%, （16.4±2.8）% and （15.8±2.5） % respectively. Meanwhile, QNZ significantly reduced the expressions of Survivin protein. Relative expression levels of Survivin in the three cell lines were 0. 58±0. 06,0. 54±0. 03 and 0.51±0.09 after treated with 10 nmol/L QNZ for 72 h. In addition, treatment with QNZ led to reduced expression o{ Bcl 2 and increased expression of Bax and cleaved Caspase-3,and thus significantly decreased the ratio of Bcl-2/Bax. Expressions of Survivin mRNA in NHL cells were inhibited by QNZ in a dose dependent manner. CONCLUSION： Inhibition of NF kB could induce cell apoptosis in hu man NHL cell lines through modulation of expressions of Survivin,Bcl 2 and cleaved Caspase-3.

关 键 词：淋巴瘤 核转录因子-KB 生存素 凋亡 

分 类 号：R733.1[医药卫生—肿瘤]