Melatonin inhibits gallbladder cancer cell migration and invasion via ERK-mediated induction of epithelial-to-mesenchymal transition.

Melatonin is a naturally occurring molecule secreted by the pineal gland that exhibits antitumor properties and prevents the development of human cancer. However, little is known regarding the effects of melatonin on gallbladder cancer (GBC) cells. The present study aimed to investigate the role of melatonin on the prevention of GBC cell invasion. The GBC cell line, GBC-SD, was treated with different concentrations of melatonin for different time periods, and the data indicated that melatonin markedly inhibited the invasion of GBC cells. Following treatment of GBC cells with melatonin, the protein levels of the epithelial marker, E-cadherin, significantly increased, while the expression levels of the mesenchymal markers, N-cadherin, Snail and vimentin, notably decreased. In addition, melatonin inhibited the phosphorylation of ERK1/2. Following treatment of the cells with the ERK activator, tert-Butylhydroquinone, the anti-invasive effects of melatonin were reversed by rescuing epithelial-to-mesenchymal transition in GBC cells. Taken together, these results suggest that melatonin inhibits GBC invasiveness by blocking the ERK signaling pathway. Thus, melatonin may be used as a potential novel cancer therapeutic drug for the treatment of GBC.