Inhibitory Effect Of Sophoridine Combined With ESI-09 On MKN45 Cells

Objective:In this study,we characterized the biology of gastric cancer cell MKN45 treated with Sophoridine and ESI-09,and analyzed its anti-apoptosis effect and regulatory effect,and to reveal the molecular mechanism.Methods:Gastric cancer MKN45 cells were cultured in vitro,and the effect of sophoridine and ESI-09 on cell proliferation were detected by CCK8 and crystal violet methods.The migration ability of MKN45 cells were detected by scratch experiment.Western blot technique was used to verify the effect of sophoridine combined with ESI-09 on the protein of p53,NF-kB p65,Nrf2,E-cadherin and N-cadherin in MKN45 cells.Flow cytometry was used to detect the effect of sophoridine combined with ESI-09 on the apoptosis of MKN45 cells.Results:1.All concentration groups of sophoridine and ESI-09,and four groups of combined drugs could significantly inhibit the proliferation of MKN45 cells in a dose-dependent manner;the combination of high,middle and low groups of sophoridine combined with ESI-09 and the high group of sophoridine combined with the middle group of ESI-09 also showed the inhibition effect on MKN45 cells,and the highest combination group was the best.2.The result of scratch test showed that all concentration groups of sophoridine and ESI-09 and significantly inhibited the migration of cells in a dose-dependent manner;the combination of high,middle and low groups of sophoridine combined with ESI-09 and the high group of sophoridine combined with the middle group of ESI-09 also showed the inhibition effect on MKN45 cells,and the highest combination group was the best.3.Selected the high dose of sophoridine combined with the middle dose of ESI-09 and two monotherapy drugs of corresponding cincentration.Western blot showed that sophoridine could up-regulate the protein level of p53,while sophoridine,ESI-09 and the combination group could down-regulate the protein level of p65,Nrf2,N-cadherin and increase the protein expression of E-cadherin.4.Selected the high dose of sophoridine combined with the middle dose of ESI-09 and two monotherapy drugs of corresponding cincentration.The results of flow cutometry showed that sophoridine,ESI-09 and the combination group could promote the apoptosis of MKN45 cells.Conclutions:1.All the concentrations of sophoridine,ESI-09 and the combination of them can inhibit the proliferation of MKN45 cells,and the combination group has the strongest inhibitory effect.2.All the concentrations of sophoridine,ESI-09 and the combination of them can inhibit the migration of MKN45 cells,and the combination group has the strongest inhibitory effect.3.Sophoridine combined with ESI-09 can inhibit the development of EMT by down-regulation the protein expression of p65 and Nrf2.4.Sophoridine combined with ESI-09 increase the apoptosis rate of MKN45 cells,showing that the anti-cancer effect may be associated with apoptosis-related pathways.