title: 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.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D064446:Orexin Receptors / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D064446:Orexin Receptors; D000068797:Orexins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3