title: Gastric cancer cell growth and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT.
abstract: The Notch signaling pathway may be important in the development and progression of several malignancies. However, the functions of Notch signaling in epithelial-mesenchymal transition (EMT) remain largely unknown. The aim of the present study was to delineate Notch1 expression in gastric cancer (GC) and its function in GC EMT. Using quantitative polymerase chain reaction and western blot analysis, the expression of Notch1 was found to increase in GC cell lines compared with the normal gastric mucosa cell line. In addition, Notch1 expression was found to be downregulated in the non-metastatic-derived GC cell line compared with the metastatic-derived cell line. Furthermore, Notch1 expression was significantly increased in the tumor tissues compared with the adjacent normal mucosa tissues, as well as in patients with metastases than in patients without metastases. To explore the role of the Notch1 signaling pathway in EMT, the GC cell lines, AGS and MKN45, were treated with γ-secretase inhibitor DAPT. Using MTT, Transwell and clonality assays, DAPT was found to inhibit the expression of the Notch1 downstream target, Hes1, and impair the ability of the GC cell lines to migrate, invade and proliferate. The protein levels of the mesenchymal markers, vimentin, neural cadherin and Snail, were decreased; however, the expression of the epithelial marker, epithelial cadherin, was increased in the GC cell lines treated with DAPT. These results indicated that the Notch1 signaling pathway may be important in the development and progression of GC. In conclusion, DAPT inhibits the Notch1 signaling pathway, as well as the growth, invasion, metastasis and EMT of GC cells.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Lu-Chun
authors.initials: LC
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Yan-Mim
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wu
keywords: Notch1; epithelial-mesenchymal transition; gastric cancer