N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.

摘要: Background/aims Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant TRAIL, thereby limiting clinical application. Therefore, there need for the development of novel adjuvant therapeutic agents be used in combination with TRAIL. Methods In this study, effect N-acetyl-glucosamine (GlcNAc), type monosaccharide derived from chitosan, combined TRAIL was evaluated vitro and vivo. Thirty NSCLC samples were detect expression death receptor (DR) 4 5. After GlcNAc co-treatment, DR determined by real-time PCR western blotting. Cycloheximide protein half-life further understand correlation between metabolic rate DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis clustering, localization visualized immunofluorescence under confocal microscope. Furthermore, co-immunoprecipitation assay performed analyze formation death-inducing signaling complex (DISC). O-linked glycan levels following DR5 overexpression RNA interference mediated knockdown. Results We found that expressed higher than DR4, co-treatment improved TRAIL-induced apoptosis activating accumulation which turn recruited apoptosis-initiating protease caspase-8 form DISC, initiated apoptosis. promoted clustering improving O-glycosylation. Conclusion These results uncovered molecular mechanism sensitizes apoptosis, highlighting effective TRAIL-mediated NSCLC-targeted therapy.