Objective:To observe the inhibitory mechanism of agrimoiin on human gastric cancer cell line HGC-27 and MKN-45.Methods:Gastric cancer HGC-27 and MKN-45 cells were divided into control group,different doses of agrimoniin groups,capecitabine(positive control)group and agrimoniin+NRF2 activator(Bardoxolone)group.Cell counting kit-8(CCK-8)assay was used to detect the viability of HGC-27 and MKN-45 cells.Scratch test was used to observe the cell migration ability.Flow cytometry was used to detect the level of intracellular re-active oxygen species(ROS).Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of malondialdehyde(MDA),glutathione(GSH)and oxidized glutathione(GSSG).Western blotting was used to de-tect the expression of PI3K-AKT pathway-related proteins and anti-ferroptosis molecules NRF2,Histone H3,HO-1,SLC7A11 and GPX4.Results:Compared with the control group,different doses of agrimoniin had a signifi-cant inhibitory effect on the activity of HGC-27 and MKN-45 cells(P＜0.05),and the inhibitory effect increased with the extension of time and the increase of agrimoniin dose.Compared with the control group,the migration ability of HGC-27 and MKN-45 cells in the low-dose and high-dose agrimoniin groups and the positive control group was weakened,the levels of ROS and MDA were increased,the ratios of GSH/GSSG,P-PI3K/PI3K,and P-AKT/AKT were decreased,and the expression of Total-NRF2,nuclear-NRF2,HO-1,SLC7A11,and GPX4 pro-teins was down-regulated(all P＜0.05).The protein expression levels of Total-NRF2 and GPX4 were increased in the agrimoniin+Bardoxolone group(P＜0.05).Conclusion:Agrimoniin can promote ferroptosis in gastric can-cer HGC-27 and MKN-45 cells,and its mechanism may be related to inhibiting the activation of PI3K-AKT-NRF2 signaling pathway.
维普
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