Effect of orexin A on apoptosis in BGC-823 gastric cancer cells via OX1R through the AKT signaling pathway

Abstract

Orexins are a class of peptides involved in the regulation of food intake, energy homeostasis, the sleep-wake cycle and gastrointestinal function. Recent studies have demonstrated that orexin A may influence apoptosis and proliferation in numerous types of cancer cells. However, the effect of orexin A on gastric cancer cells and its mechanisms of action remain elusive. In the present study, BGC-823 gastric cancer cells were treated with orexin A (10-10-10-6 M) in vitro and the expression levels of orexin receptor 1 (OX1R) protein in cells was then determined. The proliferation, viability and apoptosis of BGC-823 cells were detected. In addition, BGC-823 cells were treated with AKT inhibitor PF-04691502 or OX1R-specific antagonist SB334867 in combination with orexin A, in order to examine the activation of AKT and caspase-3. The results showed that orexin A (10-10-10-6 M) stimulated the OX1R protein expression in BGC-823 cells, which improved the proliferation and viability of the cells as well as protected them from apoptosis. Phosphorylated AKT protein was significantly increased in BGC-823 cells following treatment with orexin A. Moreover, 10-8 M orexin A reduced the proapoptotic activity of caspase-3 (by ≤30%). The OX1R antagonist SB334867 (10-6 M) and AKT antagonist PF-04691502 (10-6 M), when used individually or in combination, abolished the effect of orexin A (10-8 M) on BGC-823 cells. In conclusion, the results of the present study demonstrated that orexin A inhibited gastric cancer cell apoptosis via OX1R through the AKT signaling pathway.