Gamma secretase inhibitor impairs epithelial-to-mesenchymal transition induced by TGF-β in ovarian tumor cell lines

Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of gamma-secretase inhibition on the TGF-beta-induced epithelial mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-beta showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-beta and the gamma-secretase inhibitor DAPT. In SKOV3 and IGROVI cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zebl induced by TGF-beta. DAPT impaired the translocation of phospho-beta-catenin to the inner cell compartment observed in TGF-beta-treated cells, but was not able to block the induction at protein level induced by TGF-beta. Moreover, the inhibitor blocked the increased cell migration and invasiveness ability of both cell lines induced by TGF-beta. Notch target genes (Hes1 and Hey1) were induced by TGF-beta, decreased by DAPT treatment and remained low in the presence of both stimuli. However, DAPT alone caused no effects on most of the parameters analyzed. These results demonstrate that the gamma-secretase inhibitor used in this study exerted a blockade on TGF-beta-induced EMT in ovarian cancer cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.