Notch1信号系统对胰腺癌干细胞增殖与分化的调控

目的 探讨激活的Notch1信号系统对PANC-1胰腺癌干细胞增殖与分化的调控.方法 向体外培养的胰腺癌干细胞中分别加入Notch1激活剂rhNF-κB和抑制剂MW167,空白对照加PBS缓冲液.RT-PCR、Western印迹和流式细胞术等方法 检测Notch1信号系统的表达,及加入激活剂rhNF-κB和抑制剂MW167后,CD44和CD24的表达,以及细胞周期的变化.结果 胰腺癌干细胞中Notch信号系统的4个受体只有Notch1表达,配体只有JAG1表达;对照组的S期和G2期为21.5%和12.7%,使用MW167诱导时,细胞周期的S期和G2期所占的百分比降为17.2%和10.5%,干细胞所表达的CD44和CD24亦显著降低(P<0.05或P<0.01);而使用rhNF-κB诱导,则S期和G2期所占的百分比显著增高为29.3%和15.2%,同时CD44和CD24表达也增高(P<0.05或P<0.01).结论 当Notch信号系统被激活时,胰腺癌干细胞进行增殖;当Notch信号系统被抑制时,胰腺癌干细胞进行分化.

Regulating effect of Notch 1 signaling on differentiation and proliferation of stem cells of pancreatic adenocarcinoma

Objective To study regulation of the differentiation and proliferation of stem cells of pancreatic adenocarcinoma by activated Notch 1 signaling.Methods The rhNF-kB,an activator of Notch signaling,and the γ-secretase inhibitor Ⅱ(MW167)were added into the mediums of tumor stem cells of pancreatic adenocarcinoma respectively,and the control was added with PBS buffer.Then notch signaling was measured by RT-PCR.After intervention with rhNF-kB and MW 167,cell cycle,CD44 and CD24 were detected by Western blot and flow cytometry.Results Notch 1 and JAG 1 were expressed in stem cells of pancreatic adenocarcinoma.In the control group,21.5%and 12.7%of cells stayed at S and G2 phase.However,it decreased to 17.2%and 10.5%in MW167 group,29.3%and 15.2%in rhNF-κB group(P<0.05 or P<0.01).The expression of CD44 and CD24 of rhNF-κB group was higher than that of control group,and the effect of promoting proliferation was obvious.In contrast,the expression of CD44 and CD24 of MW167 group was decreased apparently (P<0.05 or P<0.01).Conclusion When Notch signaling is activated,the stem cells of pancreatic adenocarcinoma go on proliferating.On the contrary,the cells go on differentiating when Notch signaling is suppressed.