The proliferative effects of ghrelin on human gastric cancer AGS cells

OBJECTIVE: To investigate the role of ghrelin in the gastric cancer cell line AGS and its probable mechanism. METHODS: Cell proliferation was detected by MTT assay after treated with ghrelin or des-acyl ghrelin. The expression of growth hormone secretagogue receptor 1a (GHS-R1a) and 1b (GHS-R1b) mRNA was detected using reverse transcription polymerase chain reaction (RT-PCR). The activity of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt was measured by Western blot in cells either treated with ghrelin or inhibitors for ERK1/2 and phosphoinositide-3 kinase (PI3K). The distribution of cell cycle phases was determined by flow cytometry analysis of DNA content. RESULTS: GHS-R1a and GHS-R1b mRNA were expressed in the AGS cells. Ghrelin and des-acyl ghrelin induced AGS cell proliferation at concentrations of 1 nmol/L and 10 nmol/L but had no proliferative effect at a concentration of 100 nmol/L. The treatment of AGS cells with 10 nmol/L of ghrelin and des-acyl ghrelin resulted in the progression of the increased cells in the S phase. ERK1/2 and Akt were activated by ghrelin and des-acyl ghrelin. Specific ERK1/2 inhibitor PD98059 and PI3K inhibitor wortmannin reduced phosphorylation of ERK1/2 and Akt, respectively and blocked ghrelin- and des-acyl ghrelin-induced AGS cell proliferation. CONCLUSION: Ghrelin and des-acyl ghrelin stimulate the proliferation of gastric cancer cells via the activation of the ERK1/2 and PI3K/Akt pathway.