n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester has been researched along with Stomach-Neoplasms* in 1 studies
1 other study(ies) available for n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester and Stomach-Neoplasms
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Combination treatment of PD98059 and DAPT in gastric cancer through induction of apoptosis and downregulation of WNT/β-catenin.
γ-secretase inhibitors (GSIs), the indirect inhibitors of Notch, are emerging as a new class of anticancer agents for the treatment of solid and hematological malignancies, but little is known about their effects on gastric cancer. In this study, we demonstrate that DAPT, a potent GSI, was effective to inhibit γ-secretase activity in gastric cancer (GC) cell lines that contained a fragment with approximately the size of the Notch1 intracellular domain (NICD), but was limited in their ability to induce apoptosis. However, activation of extracellular signal-regulated kinase (ERK)1/2 upon DAPT treatment was detected. Selective inhibition of ERK1/2 activation dramatically sensitized GC cells to apoptosis via downregulating β-catenin signaling in these GC cells. Notably, in a xenograft mouse tumor model, combination therapy using ERK inhibitor PD98059 plus DAPT yielded additive antitumor effects as compared with either agent alone. Taken together, these data demonstrated that γ-secretase inhibition combined with ERK1/2 inhibitor enhances cell death in GC cells partly through downregulation of WNT/β-catenin pathways. Topics: Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; beta Catenin; Cell Line, Tumor; Dipeptides; Down-Regulation; Female; Flavonoids; Humans; Male; MAP Kinase Signaling System; Mice, Nude; Middle Aged; Receptor, Notch1; Stomach Neoplasms; Wnt Proteins | 2013 |