title: [Effects of gastrin receptor antagonist and cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cell].
abstract: OBJECTIVE
  To investigate the regulative roles of the gastrin receptor antagonist proglumide and the specific cyclooxygenase (COX)-2 inhibitor NS-398 on the proliferation and apoptosis of gastric cancer cells.
  
  
  METHODS
  Human gastric cancer cells of the line MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. Subconfluent cell cultures were treated with proglumide at a final concentration of 5 mmol/L, NS-398 at a final concentration of 10.0 micromol/L, or proglumide in combination with NS-398 for 48 h. The growth and proliferation of MKN-45 cells were analyzed with MTT assay. Flow cytometric analysis was used to detect the apoptosis of the gastric cancer cells. RT-PCR and Western blotting were used to detect the expression of apoptosis-inhibited gene bcl-2 mRNA and protein.
  
  
  RESULTS
  The apoptosis rates of the cells treated by proglumide, NS-398, and combination of two agents were 24.7% +/- 3.2%, 26.7% +/- 3.4%, and 36.1% +/- 4.6% respectively, all significantly higher than that in the control group (1.6% +/- 0.6%, all P < 0.01). The apoptosis rates of the MKN-45 cells treated with proglumide combined with NS-398 was significantly greater than those of the cells treated by the two agents alone (both P < 0.05). Treatment with proglumide and NS-398 significantly reduced the bcl-2 mRNA and protein expression in the MKN-45 cells (P < 0.05).
  
  
  CONCLUSIONS
  Both proglumide and NS-398 inhibit the proliferation and induce the apoptosis of human gastric cells. This apoptosis may be mediated by down-regulation of the expression of apoptosis-inhibited gene bcl-2. Co-treatment with proglumide and NS-398 have synergistic anticancer role.
authors: Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Wei-hao
authors: WH
authors: Sun
authors: Han
authors: H
authors: Su
authors: Li-jiu
authors: LJ
authors: Zhang
authors: Yun
authors: Y
authors: Shao
authors: Hai-chen
authors: HC
authors: Xu
authors: Tao
authors: T
authors: Zhang
authors: Yi-ping
authors: YP
authors: Xue
authors: Guo-xian
authors: GX
authors: Ding
authors: Yun-lin
authors: YL
authors: Cheng