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.


CONCLUSIONS
Ghrelin and des-acyl ghrelin stimulate the proliferation of gastric cancer cells via the activation of the ERK1/2 and PI3K/Akt pathway.
Department of Gastroenterology, Jinshan Hospital, Fudan University, Shanghai Medical College of Fudan University, Shanghai, China.
Pei Ying
PY
Tian
Xiao Ming
XM
Fan
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D054440:Receptors, Ghrelin / Q000235:genetics; D013274:Stomach Neoplasms / Q000473:pathology*
D054439:Ghrelin; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; C422650:ghrelin, des-n-octanoyl; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases