Effects on Cell Proliferation, Invasion and Migration of Esophageal Adenocarcinoma by Inhibition of Notch and PI3K /Akt Pathway

Objective To investigate the effects of Notch and PI3K/Akt pathways on cell proliferation, invasion and migration abilities of esophageal adenocarcinoma cell lines OE33 and the association between the two signaling pathways.

Methods DAPT as an inhibitor of Notch1 signaling pathway and LY294002 as an inhibitor of PI3K/Akt signaling pathway were given alone and in combination to OE33 cells. Control group were the cells treated without drug. The change of NICD, Hes1, p-Akt and PTEN protein and mRNA expression in OE33 cells were analyzed by Western blot and Real-time Quantitative PCR. The abilities of cell proliferation, migration and invasion were measured respectively by CCK-8, Wound healing assay and Transwell invasion assay.

Results DAPT reduced the protein expression levels of NICD and Hes1, while increased the protein expression of p-Akt; LY294002 not only reduced the protein expression of p-Akt but also down-regulated the protein expression of Hes1, meanwhile, up-regulated the level of NICD protein and Hes1 mRNA. Blocking both two pathways resulted in the down-regulation of NICD, Hes1 and p-Akt proteins expression. The combination of two blockers significantly inhibited the abilities of cells proliferation, migration and invasion, compared with the control and single drug treatment group. PTEN protein and mRNA expression levels in each treatment group had increased to some extent.

Conclusion The interactions may exist between Notch-1 and PI3K/Akt signaling pathways in OE33 cells, meanwhile, the dual inhibition could effectively weaken the proliferation, invasion and migration of OE33 cells.