γ secretase inhibitor dapt  (MedChemExpress)

Journal: eBioMedicine

Article Title: Differential regulation of FADS2 by EZH2 reveals a metabolic vulnerability in ovarian cancer treatment

doi: 10.1016/j.ebiom.2025.105879

Figure Lengend Snippet: Co-inhibition of EZH2 and FADS2 inhibitors induces synergistic inhibition of Notch signalling and mitochondrial function. a and b, Protein levels of NICD1, c-Myc and HES1 in ovarian cancer cells treated with GSK126 (10 μM) or EPZ6438 (40 μM) combined with SC26196 (30 μM) for 48 h, as detected by western blotting. c, Protein levels of NICD1, c-Myc and HES1 in SKOV3 EZH2-KO and EZH2-WT cells stably transfected with shFADS2 and in A2780 cells stably transfected with shFADS2 were detected by western blotting. d, Activation of the AMPK pathway and Notch1 signalling and protein levels of SDHD in ovarian cancer cells treated with Nirogacestat (10 μM), oligomycin (1 μM) or the combination of both for 48 h, as detected by western blotting. e, Protein levels of EZH2 and H3K27me3 in ovarian cancer cells treated with nirogacestat (10 μM), oligomycin (1 μM) or both for 48 h, as detected by western blotting. f, Protein levels of EZH2, p21, and AMPK in ovarian cancer cells treated with SC26196 (30 μM), Compound C (5 μM) or the combination of both for 48 h, as detected by western blotting. g, Proposed model of combined targeting of EZH2 and FADS2 to treat ovarian cancer via synergistic inhibition of Notch signalling and mitochondrial function.

Article Snippet: The FADS2 inhibitor SC26196, the PROTAC EZH2 degrader-1, the AMPK inhibitor compound C (dorsomorphin), the γ-secretase inhibitor nirogacestat, MG132, cycloheximide, and oligomycin were purchased from MedChemExpress.

Techniques: Inhibition, Western Blot, Stable Transfection, Transfection, Activation Assay