Orexin A upregulates the protein expression of OX1R and enhances the proliferation of SGC-7901 gastric cancer cells through the ERK signaling pathway

Orexins are hypothalamic peptides that regulate food intake, wakefulness, the reward system and energy metabolism. Recent studies have demonstrated the ability of orexins to promote a robust apoptosis and subsequent inhibition of cell growth in various types of cancer cells. The present study was conducted to investigate the effects of orexin A on the survival of human gastric cancer cells, SGC-7901, and the possible mechanisms. SGC-7901 cells were exposed to various concentrations of orexin A in vitro in the presence or absence of the orexin receptor 1 (OX1R) antagonist (SB334867), extracellular signal-regulated kinases 1 and 2 (ERK1/2) antagonist (U0126) or a combination of the two antagonists. The amount of cell proliferation, viability and apoptosis, caspase-8 and caspases-9 activities, OX1R protein expression and ERK1/2 protein levels were determined. The expression of OX1R in SGC-7901 cells was observed. Orexin A (10(-10) to 10(-6) M) stimulated SGC-7901 cell proliferation and viability, reduced the pro-apoptotic activity of caspase-9 and protected the cells from apoptosis in a dose-dependent manner: Additionally, ERK1/2 phosphorylation was stimulated by orexin A (1040 to 10(-6) M). However, the OX1R antagonist SB334867 (10(-6) M), ERK1/2 antagonist U0126 (30 mu M) or the combination of antagonists blocked the effects of orexin A to a certain extent. These results suggest that stimulation of OX1R induces the growth of SGC-7901 gastric cancer cells through activation of ERK1/2 signaling pathway. These findings add a new dimension to the biological activities of orexin, which may have important implications in health and disease, in particular gastric cancer.