The Effect Of Notch1 Signaling On The Biological Characteristics Of Hepatocellular Carcinoma Cells And Lung Cancer Epithelial Cells

Notch signaling involved in a variety of cell specification, proliferation and apoptosis. Our studies for the first time demonstrated that the constitutively active Notch 1 and downstream factor Deltex1 can inhibit the growth of human hepatocellular carcinoma cells in vitro and in vivo and regulate the cytokines and chemokines secretion in lung cancer epithelial cells. The related mechanisms of HCC cells growth inhibition was involved in alteration of some cell cycle regulated proteins and Bcl-2 expression. Synergistic induction of apoptosis by Notchl and TRAIL in SMMC7721 cells maybe related to the PI3K/pAkt, NF-kB inhibition and caspase3 cascade activation. In addition, Notchl signaling could induce the inflammatory mediators in A549 cells possibly through NF-kB and Smad3 activation. LPS and LTA stimulation affect the secretion of cytokines and the effects maybe correlated with (Notchl) ICN degradation and activation of p38, Smad3 and IL-10 promotor. Our results provided new evidence for the mechanisms of Notchl signaling involved in regulating apoptosis and growth in HCC cells and propose the possibility that dysregulation of Notchl signaling may participate in the lung inflammation and development of lung cancer. The data of these studies also provide new clue for the potential role of Notch signaling in the treatment of malignancy.