Akt-dependent NF-κB activation is required for bile acids to rescue colon cancer cells from stress-induced apoptosis

摘要: Conjugated secondary bile acids promote human colon cancer cell proliferation by activating EGF receptors (EGFR). We hypothesized that acid-induced EGFR activation also mediates survival downstream Akt-regulated of NF-κB. Deoxycholyltaurine (DCT) treatment attenuated TNF-α-induced apoptosis, and stimulated rapid sustained NF-κB nuclear translocation transcriptional activity (detected binding to an oligonucleotide consensus sequence luciferase reporter gene constructs). Both DCT-induced attenuation TNF-α-stimulated apoptosis were dependent on activation. Inhibitors translocation, proteosome activity, IκBα kinase activity. Cell transfection with adenoviral vectors encoding a non-degradable ‘super-repressor’ blocked the actions DCT both apoptosis. Likewise, mutant akt chemical inhibitor Akt effects Chemical inhibitors rescue H508 cells from ultraviolet radiation-induced Collectively, these observations indicate that, EGFR, is mediated Akt-dependent These findings provide mechanism whereby increase resistance chemotherapy radiation.