Proglumide And Aspirin Co-inhibit Proliferation Of Human Colon Cancer Cell Line HT-29

Objective:To Investigate the gastrin receptor antagonist proglumide and non-steroidal anti-inflammatory drugs aspirin co-inhibiting mechanism on growth and proliferation of cultured human colon cancer cell line HT-29.Methods:Applying proglumide and aspirin on cultured human colon cancer cell line HT-29 separately and jointly,Using MTT colorimetric assay on detection of growth and proliferation of HT-29 cells,real-time quantitative reverse transcription polymerase chain reaction(Real-time PCR) on detection of COX-2 and 15-PGDH mRNA's expressions,protein blotting(Western-blot) on detection of COX-2 and 15-PGDH protein's expressions.Results:Proglumide and aspirin,respectively,both time and dose-dependently inhibit HT-29 cells' growth and proliferation,and both have a synergistic inhibitory effect. With proglumide alone intervening,COX-2 mRNA and protein's expressions of HT-29 cells,turn lower than that of normal control group;while 15-PGDH mRNA and protein's expressions turn higher than the normal control group;and proglumide group,comparing to normal control group,is statistically significant(P＜0.05).With aspirin alone intervening,COX-2 mRNA and protein's expressions of HT-29 cells decrease,while the 15-PGDH mRNA and protein's expressions increase,comparing to the normal control group;but the aspirin group,comparing to the normal control group,is not statistical significant.With proglumide and aspirin combined intervening, COX-2 mRNA and protein's expressions decrease significantly,and 15-PGDH mRNA and protein's expressions increase significantly;and the united drug group, comparing to the normal control group and a separate drug group is statistically significant(P＜0.05).Conclusions:Gastrin receptor antagonist proglumide inhibits the growth and proliferation of cultured colon cancer HT-29 cells by inhibiting the expression of COX-2 and promoting the expression of 15-PGDH.Non-steroidal anti-inflammatory drug aspirin inhibits the growth and proliferation of HT-29 cells perhaps in the COX-2 and non-COX-2 ways.When proglumide and aspirin are combined,there is a synergistic inhibition on growth and proliferation of HT-29 cells,which is partly through inhibiting COX-2 expression and promoting 15-PGDH expression;aspirin inhibiting COX-2 expression collaborated with proglumide,further implys that COX-2 may be one of the downstream objectives of gastrin.