Regulating effect of Notch 1 signaling on differentiation and proliferation of stem cells of pancreatic adenocarcinoma / 中华肝胆外科杂志

ABSTRACT

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.