Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via Calpain-mediated C/EBPβ and NFκB cleavage.

摘要: Peritoneal dissemination of tumor has high mortality and is associated with the loss epithelial features, acquisition motile mesenchymal morphology characteristics, invasive properties by cells. Melatonin an endogenously produced molecule in all plant species that known to exert antitumor activity, but date, its underlying mechanisms antiperitoneal metastasis efficacy not well defined. This study determined potential melatonin vivo assessed association inhibition epithelial-to-mesenchymal transition (EMT) signaling mechanism endoplasmic reticulum (ER) stress, which may be a major molecular against cancer. The results demonstrate inhibited peritoneal activated ER stress Cignal ERSE Reporter Assay, organelle structure transmission electron microscopy images, calpain protein biomarkers like p-elf2α. Moreover, overexpression transcription factor C/EBPβ gastric cancer interacted NFκB further regulates COX-2 expression. These were dissociated downregulated melatonin, as proven immunofluorescence imaging, immunoprecipitation, EMSA, ChIP assay. or gene silencing decreased EMT markers (E-cadherin, Snail, Slug) Wnt/beta-catenin activity Topflash increased markers. In animal study, therapy consistent those vitro findings attenuated systemic proangiogenesis production. conclusion, impede both growth inducing inhibiting EMT.