激活Notch信号抑制多发性骨髓瘤细胞凋亡

摘要多发性骨髓瘤(multiple myeloma，MM)细胞的增殖及凋亡受骨髓造血微环境的调节。Notch信号是骨髓中细胞与细胞之间通讯的主要信号通路之一，它对多发性骨髓瘤细胞的调节作用目前并不清楚。本研究旨在阐明Notch信号对多发性骨髓瘤细胞凋亡的调节作用。利用RT-PCR分析多发性骨髓瘤细胞Notch信号分子的表达和采用逆转录病毒介导的基因转移方法将Notch-1胞内区(Intracellular domain of Notch，ICN)转入多发性骨髓瘤细胞株，以建立激活)Notch信号的多发性骨髓瘤细胞系；采用台盼蓝拒染和TUNEL方法测定骨髓瘤细胞的死亡。结果表明：RT-PCR检测显示多发性骨髓瘤细胞表达、Notch-1及相关分子。逆转录病毒可以介导外源Notch-ICN在骨髓瘤细胞中表达，激活Notch-1信号可以抑制二甲基鞘氨醇(N，N-dimethylspingosine，DMS)诱导的多发性骨髓瘤细胞的凋亡。结论：：Notch信号对多发性骨髓瘤细胞凋亡有抑制作用，这可能为多发性骨髓瘤的治疗提供新的靶点．

Suppressive Effect of Notch Signal Activation on Apoptosis of Multiple Myeloma Cells

The proliferation and apoptosis of multiple myeloma (MM) cells were regulated by bone marrow microenvironments in which Notch signal plays important role in mediating cell-cell communication. However,the regulatory effect of Notch signal on the proliferation and apoptosis of multiple myeloma cells remains unclear. In this study,regulatory effect of Notch signal on the apoptosis of MM cells induced by DMS (N,N-dimethylsphingosine) was investigated. RT-PCR was used to identify the expression of Notch receptor and related molecules such as Dll-1,Jagged-1,Deltex-1 in MM cell lines. The intracellular domain of Notch (ICN),active form of Notch,was transferred into MM cells by retrovirus. The apoptosis of MM cells was determined by typan blue exclusion tests and TdT-mediated dUTP nick end labeling (TUNEL) assay. The results showed that multiple myeloma cells expressed the Notch-1 and its related molecules. Notch activated multiple myeloma cell lines were obtained. Activation of Notch protected the multiple myeloma cells from the apoptosis induced by DMS,which was determined by cell viability and TUNEL assay. In conclusion, Notch signal suppressed the apoptosis of multiple myeloma cells and would possibly be a novel therapeutic target.