摘要
The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.
基金
the National Natural Science Foundation of China(No.81801621,No.81572723,No.81872253).
