Notchl信号系统对胰腺癌干细胞增殖与分化的调控  

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

作　　者：黄鹏[2] 王春友[1] 吴河水[1] 熊炯炘[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胰腺外科,武汉430022 [2]咸宁学院附属第一医院普外科,湖北437100

出　　处：《中华肝胆外科杂志》2010年第5期359-362,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：基金项目：本课题受国家自然科学基金资助（基金编号30571817）

摘　　要：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.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.

关 键 词：胰腺肿瘤 NOTCH信号 肿瘤干细胞 增殖 分化 

分 类 号：R735.9[医药卫生—肿瘤]