Activating the Wnt/β-Catenin Pathway for the Treatment of Melanoma – Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3
Fig 3
Cell death induced by LY2090314 is dependent on β-catenin and GSK3β knockdown increases the sensitivity of cells to LY2090314.
A. Melanoma cells stably transfected with shRNAs targeting β-catenin display decreased β-catenin and Axin2 protein expression by western blot. A375 (B) and M14 (C) cells expressing shRNAs targeting β-catenin (● Control; ■ β-catenin shRNA 1; ▲ β-catenin shRNA 2; ▼ β-catenin shRNA 3) become resistant to LY2090314 suggesting that β-catenin is required for apoptotic cell death in response to LY2090314. D, E. A375 cells targeted with GSK3β shRNA, but not GSK3α shRNA, demonstrates increased sensitivity to LY2090314 (4.5nM, 72hr).