Effects Of Gastrin On The Proliferation And Cyclooxygenase-2 Expression In Gastric Cancer Cell

Backgroud Gastric cancer is one of the most common human malignant diseasesand remains the leading cause of cancer-related mortality in our country. Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, the mechanisms of how gastrin receptor antagonist mediatesits anticancer effects remain unclear.Objective To investigate the regulative role of gastrin and a gastrin receptor antagonist proglumide on the cell proliferation and COX-2 expression in a gastric cancer cell line,SGC-7901.Methods SGC-7901 cells were seeded in RPMI-1640 supplemented with 10%heat-inactivated fetal calf serum and routinely incubated for 24h. After serum-free starvation for 24h, the cells were cultured with either gastrin at the final concentration of 0.1, 1, 10 and 100nmol/L or 100nmol/L gastrin plus proglumide at the final concentration of 1, 10, 100 and 1000μmol/L for 24h, 48h and 72h respectively. The cell proliferation was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. Expression of COX-2 protein level was measured with Western blot analysis.Results Gastrin increased SGC-7901 cell proliferation in a dose- and time-dependent manner. Gastrin receptor antagonist proglumide significantly inhibited SGC-7901 cell proliferation induced by gastrin. Gastrin increased the expression of COX-2 in SGC-7901 cells. Proglumide abolished the up regulation of COX-2 expression induced by gastrin.Conclution This study demonstrates that gastrin stimulate gastric cancer cell proliferation via upregulation of COX-2 expression through the activation of the gastrin receptor.