Effect Of Esomeprazole On Proliferation Of Gastric Cancer AGS Cells And Its Relationship With The Expression Of Akt And EGFR

ObjectiveTo investigate the effects of esomeprazole on the proliferation of human gastric cancer AGS cell line and its relationship with protein kinase B(Akt),epidermal growth factor receptor(EGFR),Caspase-3 and Caspase-7.To explore its possible mechanism,and to provide the individualized treatment of gastric cancer with esomeprazole.MethodsThe effects of esomeprazole alone and associated with AKT agonist,EGFR inhibitor on the proliferation of human gastric cancer AGS cell line were detected by CCK-8 assay.RT-PCR,Western blot technology were used to detect the relative changes of Akt,EGFR,Caspase-3,Caspase-7 mRNA and protein expression.Result1.Human gastric cancer AGS cell line was treated with different concentrations(0 mg/L,5 mg/L,10 mg/L,20 mg/L,40 mg/L,60 mg/L,80 mg/L,100 mg/L,120 mg/L)of esomeprazole for 48 hours.The inhibition rate(0.00%,4.44%,5.72%,7.98%,31.82%,52.31%,74.26%,86.29%,95.41%)of human gastric cancer AGS cell proliferation was increased in concentration dependent manner of esomeprazole,which was statistical significance compared with the control group(P <0.01).Esomeprazole(40mg/L)combined with different concentrations(0?M,20?M,50?M,100?M)of EGFR inhibitors were used to treat human gastric cancer AGS cells for 48 h.The inhibition rate of human gastric cancer AGS cells proliferation increased gradually with the increase of EGFR inhibitor concentration(0.00%,31.82%,43.76%,46.46%,49.41%).There was statistical significance compared with the control group(P <0.01).Esomeprazole(40mg/L)combined with different concentrations(0?M,20?M,50?M,100?M)of Akt agonist were used to treat human gastric cancer AGS cells 48 h.With the increase of Akt agonist concentration,The inhibition rate of human gastric cancer AGS cell proliferation were increased gradually(0.00%,31.61%,47.99%,51.88%,52.61%),There was statistical significance compared with the control group(P <0.01).2.The expression of Akt,Caspase-3 and Caspase-7 mRNA decreased while the expression of EGFR mRNA increased after the AGS was treated with esomeprazole(40mg/L)for 48 h.3.The expression of Akt,Caspase-3 and Caspase-7 protein decreased and the expression of EGFR protein increased after the AGS was treated with esomeprazole(40mg/L)for 48 h.With the increase of the concentration of esomeprazole,the expression of Akt protein decreased gradually and the expression of EGFR protein increased gradually in human gastric cancer AGS cells after they were treated with esomeprazole of different concentrations(0 mg/L,2.5 mg/L,5 mg/L,10 mg/L,20 mg/L,40mg/L)for 48 h.With the increase of EGFR inhibitor of different concentrations(0?M,20?M,50?M,100?M),the expression of Akt,EGFR protein decreased gradually and the expression of Caspase-3,Caspase-7 protein increased gradually in human gastric cancer AGS cells after they were treated with EGFR inhibitor for 48 h.Esomeprazole(40mg/L)combined with different concentrations(0?M,20?M,50?M,100?M)EGFR inhibitors were used to treat human gastric cancer AGS cells for 48 h.With the increase of the concentration of EGFR inhibitor,the expression of Akt,Caspase-3 and Caspase-7 protein increased gradually and the expression of EGFR protein decreased gradually.With the increase of Akt agonist of different concentrations(0?M,20?M,50?M,100?M),the expression of Akt,Caspase-3 and Caspase-7 protein increased gradually and the expression of EGFR protein decreased gradually in human gastric cancer AGS cells after they were treated with Akt agonist for 48 h.Esomeprazole(40mg/L)combined with different concentrations(0?M,20?M,50?M,100?M)Akt agonist were used to treat human gastric cancer AGS cells 48 h.With the increase of the concentration of Akt agonist,the expression of Akt protein increased gradually and the expression of EGFR protein decreased gradually,while the change trend of the expression of Caspase-3,Caspase-7 was not obvious.Conclusions1.Esomeprazole can inhibit the proliferation of human gastric cancer AGS cells,and the inhibition rate is increased in concentration dependent manner of esomeprazole in a certain extent.2.Esomeprazole combined with different concentrations of Akt agonists and EGFR inhibitor inhibite the proliferation of human gastric AGS cells,and the inhibition rate is increased in concentration dependent manner of Akt agonists and EGFR inhibitor.3.The inhibitory effect of esomeprazole on the proliferation of human gastric cancer AGS cells may be related to the expression of Akt decreased and the expression of EGFR increased.