阻断Notch1信号抑制多发性骨髓瘤细胞增殖临床研究

目的探讨γ-分泌酶抑制剂(GSI)对RPMI8226细胞Notch1信号通路的作用及对细胞生长增殖影响。方法采用细胞生长曲线绘制和MTT法检测细胞生长与增殖,Western印迹分析Notch1的活化形式和靶基因Hes-1蛋白表达的改变。结果GSI可抑制细胞生长和增殖,呈时间依赖效应,72 h抑制作用最明显。Notch1和Hes-1在RPMI8226细胞中高表达,GSI作用后均明显下调。在24、48、72 hGSI对RPMI8226细胞、Notch1蛋白分别下调至作用前的(65.0±3.7)%、(45.4±5.7)%和(25.0±4.2)%,而Hes-1蛋白表达分别下调至作用前的(70.9±10.1)%、(50.7±5.2)%和(30.3±6.6)%。结论GSI可有效地阻断Notch1信号通路,抑制RPMI 8226细胞生长增殖。

Blocking Notch1 Signaling Inhibits Proliferation of Multiple Myeloma Cells

Objective To investigate the role of the specific γ-secretase inhibitor(GSI) on Notch1 and its effect on proliferation in multiple myeloma cell line RPMI8226.Methods The cell growth curve was drawn and the cell proliferation was measured by MTT assay.The expression of Notch1 activation form(N1-ICD) and Hes-1 protein was detected by Western blot.Results GSI can inhibit cell growth and proliferation in a time-dependent manner in multiple myeloma cell line and the inhibiting effects is the most obvious in the group of 72 h.Compared with the control group,RPMI8226 cell treated with GSI at time of 24,48 and 72 h showed the decrease of N1-ICD to(65.0±3.7)%,(45.4±5.7)%and(25.0±4.2)% respectively,and Hes-1 expression to(70.9±10.1)%,(50.7±5.2)% and(30.3±6.6)% respectively.Conclusion GSI effectively blocks Notch1 signal and inhibits cell growth and proliferation.