Effects Of Specific COX-2 Inhibitor And Gastric Receptor Antagonist On Proliferation And Apoptosis Of Gastric Cancer

Objective: Considerable evidences suggest that cyclooxygenase-2 (COX-2) and gastrin play very important roles in occurrence, progression and prognosis of tumor. But the definite effects and mechanisms of special COX-2 inhabitor and gastrin receptor antagonist on the growth of gastric cancer have not been fully elucidated. The aims of present study were to investigate the effects and mechanisms of a special COX-2 inhabitor (NS-398) and a special gastrin receptor antagonist (AG-041R) on the proliferation and apoptosis in a gastric cancer cell line, MKN-45; To emphasizely observe the effects and mechanisms of combination treatment with NS-398 and AG-041R on antiproliferation and induction of apoptosis in MKN-45; To investigate the elementary mechanism of the synergic effect of combination treatment with NS-398 and AG-041R on antiproliferation and induction of apoptosis in MKN-45 so as to support the experimental bases. Methods: MKN-45 cells were incubated in the medium with NS398, AG-041R and the combination of these two agents, respectively. Cell growth and proliferation of MKN-45 were analyzed with MTT assay; apoptosis was detected with flow cytometry assay; C-myc mRNA was determined by RT-PCR. Results: 1. NS-398 and AG-041R inhibited cell growth of MKN-45 in a time and dose dependent manner at a concerntration of 1(10-8 to 1(10-5 mol/L, 1(10-9 to 1(10-6 mol/L, respectively. Combination with 1(10-5 mol/L NS-398 and 1(10-6mol/L AG-041R inhibited the proliferation more remarkably than either agent applied singly (P<0.01), analyzation with Jin Zheng- jun,s method suggested that q>1.15, and the inhibition rate enhanced with the prolong of time. 2. Apoptosis cell group, Sub-G1 peak could be observed by NS-398 of 1(10-5 mol/L, AG-041R of 1(10-6 mol/L and combination group in 72h, the percentage of apoptosis was (9.57±0.60)%, (10.25±0.68)% and (20.83±1.90)% respectively. The apoptosis rate of combination group was much greater than that of the two agents applied singly (P<0.01). 3. NS-398 and AG-041R could down-regulate the level of c-myc mRNA respectively (P<0.01); the combination group could down-regulate the level of c-myc mRNA significantly than the two agents applied respectively (P<0.01).Conclusion: 1. NS-398 and AG-041R inhibit MKN-45 from growing in a time and dose dependent manner in a range respectively; the growth of MKN-45 was inhibited more remarkably by NS-398 in combination with AG-041R in a synergistic manner; 2. Both NS-398 and AG-041R induced the apoptosis of MKN-45 remarkably; the apoptosis rate of combination group was much greater than that of the two agents applied singly. 3 NS-398 and AG-041R could down-regulate the level of c-myc mRNA respectively; the combination group could down-regulate the level of c-myc mRNA significantly than the two agents applied respectively.