Notch信号分子在人淋巴瘤细胞中的表达及意义  

Expression of Notch Signal Molecules in Human Lymphoma Cells and Its Significance

作　　者：王艳芳[1] 李艳莹[1] 王晶[1] 克晓燕[1] 

机构地区：[1]北京大学第三医院血液科,北京100191

出　　处：《中国实验血液学杂志》2012年第1期83-87,共5页Journal of Experimental Hematology

摘　　要：本研究探讨Notch信号分子在人淋巴瘤细胞中的表达及其意义。选择人B淋巴瘤细胞系(Raji、Maver、Z138)和T淋巴瘤细胞系Jurkat细胞,利用RT-PCR技术检测Notch信号分子在这些细胞中的表达情况;利用流式细胞术检测γ-分泌酶抑制剂DAPT阻断Notch信号后对淋巴瘤细胞凋亡以及细胞周期的影响;利用CCK-8法检测DAPT对淋巴瘤细胞增殖的影响。结果表明:Notch分子在不同淋巴瘤细胞中的表达有所不同,Notch1和Notch2在4种细胞中均有表达,Notch3主要表达于Jurkat细胞,而Notch4仅在Raji细胞中弱表达;另外,Notch下游靶基因Hes1仅表达于Raji和Jurkat细胞。DAPT对Jurkat和Raji细胞的增殖抑制以及凋亡诱导作用比较明显,并将细胞周期阻滞在G1期,但是对Maver和Z138细胞的作用较弱。DAPT可以通过抑制Notch下游靶基因Hes1的表达而发挥作用。结论:Notch信号的异常表达与活化对淋巴瘤细胞的增殖起着重要作用,Notch信号有望成为淋巴瘤治疗的一个新靶点。The study was aimed to investigate the expression of Notch signal molecules in human lymphoma cells and its significance. Raji, Maver, Z138 and Jurkat cell lines were used in the study. RT-PCR was used to determine the expression of Notch signaling molecules in these lymphoma cells. Flow cytometry was used to detect the apoptosis and cell-cycle of the lymphoma cells induced by different concentrations of gamma secretase inhibitor DAFT. CCK-8 was used to detect the proliferation of the lymphoma cells treated by DAPT. The results showed that the expression of Notch molecules in the four cell lines was different. Notchl and Notch2 were found to be expressed in the four lymphoma cell lines, Notch3 predominantly expressed in Jurkat ceils, Notch4 only expressed in Raji cells weakly and Hesl only expressed in Raji and Jurkat cells. Treatment with DAPT could increase the apoptosis ratio of Raji and Jurkat cells. Besides, DAPT could significantly inhibit the proliferation of Raji and Jurkat cells by inducing the cell cycle arrest in G~ phase, but the effect of DAPT on Mayer and Z138 ceils was not obvious. The activity of Notch pathway could be inhibited by DAPT treatment through down-regulating the expression of Notch target gene Hesl. It is concluded that the abnormal expression and activation of Notch signal pathway play an important role in the proliferation of lymphoma cells. Notch may be likely a new target for the therapy of lymphoma.

关 键 词：NOTCH信号通路 淋巴瘤 Γ-分泌酶抑制剂 细胞凋亡 细胞周期 

分 类 号：R733.1[医药卫生—肿瘤]