Melatonin inhibits epithelial-to-mesenchymal transition in gastric cancer cells via attenuation of IL-1 beta/NF-kappa B/MMP2/MMP9 signaling

摘要

Although melatonin has been shown to exert marked antitumor effects against a variety of cancers, the underlying mechanisms remain to be fully elucidated. It has been hypothesized that the anticancer properties of melatonin are associated with its ability to suppress epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, melatonin effectively suppressed interleukin (IL)-1 beta-induced EMT in human gastric adenocarcinoma (GA) cells. Sequential treatment of GA cells with melatonin after IL-1 beta challenge markedly reversed the IL-1 beta-induced morphological changes, reduced cell invasion and migration, increased beta-catenin and E-cadherin expression, and downregulated fibronectin, vimentin, Snail, matrix metalloproteinase (MMP)2 and MMP9 expression. Moreover, IL-1 beta-induced activation of NF-kappa B was attenuated following treatment with melatonin. Knockdown of NF-kappa B significantly reduced the IL-1 beta-induced EMT in GA cells. Taken together, these findings indicate that melatonin may act by suppressing EMT and tumor progression by inhibiting NF-kappa B activity.