LYTAK1, a novel TAK1 inhibitor, suppresses KRAS mutant colorectal cancer cell growth in vitro and in vivo

摘要: KRAS mutation in colorectal cancer (CRC) activates transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) to promote tumor progression. In the current study, we explored potential effect of LYTAK1, a novel TAK1 inhibitor, against mutant CRC cells vitro and vivo. We found that LYTAK1 dose-dependently inhibited cell (HT-29 SW-620 lines) growth, induced cycle G1-S arrest. Further, activated apoptosis HT-29 cells, inhibitors almost reversed LYTAK1-mediated inhibition. While wild-type (WT) lines (DLD-1 HCT-116), had no on progression, or apoptosis. SW-260 blocked activation phosphorylation at Thr-184/187. Activation nuclear factor κB (NF-κB) these detected by phosphorylations p65 IκB α (IKKα) as well expression NF-κB-regulated gene cyclin D1, was significantly LYTAK1. treatment resulted downregulation β-catenin Wnt response Axin 2, indicating inactivation. vivo, oral xenograft nude mice. Together, results show inhibits both might be investigated agent with mutation.