Objective Observation of the effect of magnolol on ferroptosis in gastric cancer mice and exploration of its mechanism.Methods A total of 24 mice were randomly divided into a control group,a magnolol group,an iron death inhibition group,and an iron death excitation group according to the block randomization method,with 6 mice in each group,to establish a gastric cancer cell line tumor bearing mouse model.Obtain tumor weight/body weight ratio,liver index,kidney index,and spleen index after continuous administration for 8 weeks;Immunohistochemical staining was used to measure the expres-sion of proliferating cell associated antigen(Ki-67)and proliferating cell nuclear antigen(PCNA-1)in tumor tissue;Enzyme linked immunosorbent assay(ELISA)was used to measure the levels of glutathione peroxidase 4(GPX4),malondialdehyde(MDA),and superoxide dismutase(SOD)in tumor tissue;Immu-noblotting was used to measure the protein expression of acyl CoA synthase long chain 4(ACSL4),trans-ferrin receptor(TFRC),Yes related protein 1(YAP-1),and Phosphorylation YAP1(p-YAP1)in tumor tissues.Results The tumor weight/body weight ratio of the Houpo phenol group was lower than that of the control group(2.99±0.97 vs.5.02±0.83,t=0.096,P＜0.05),and the spleen index was higher than that of the control group(0.25±0.07 vs.0.19±0.03,t=0.087,P＜0.05);The tumor weight/body weight ratio of the iron death inhibition group was higher than that of the honokiol group(4.33±0.96 vs.2.99±0.97,t=0.092,P＜0.05)and the spleen index was lower than that of the honokiol group(0.14±0.04 vs.0.25±0.07,t=0.073,P＜0.05);The tumor weight/body weight ratio of the iron death activation group was lower than that of the honokiol group(2.01±0.42 vs.2.99±0.97,t=0.081,P＜0.05).The expression of Ki-67 and PNCA-1 in the tumor tissue of the honokiol group was lower than that of the control group(9.35±2.32,10.65±2.14 vs.15.37±3.86,16.23±4.62,t=1.463,1.003,P＜0.05);The expression of Ki-67 and PNCA-1 in tumor tissues of the iron death inhibition group was higher than that of the honokiol group(13.81±3.78,14.01±5.26 vs.6.51±3.12,7.73±1.89,t=0.163,0.520,P＜0.05);The expression of Ki-67 and PNCA-1 in tumor tissues of the iron death ex-citation group was lower than that of the honokiol group(8.76±3.54,11.25±2.92 vs.16.51±2.71,15.21±3.85,t=1.623,1.152,P＜0.05).The MDA level in the tumor tissue of the honokiol group was higher than that of the control group[(14.76±3.57)μmol/mg vs.(8.72±2.08)µmol/mg,t=1.261,P＜0.05],while the GPX4 and SOD levels in the tumor tissue of the honokiol group were lower than those of the control group[(5.15±2.34)mU/mg,(6.08±3.41)U/mg vs.(11.07±1.82)mU/mg,(13.63±2.09)U/mg,t=0.893,0.765,P＜0.05];The MDA level in the tumor tissue of the iron death inhibition group was lower than that of the honokiol group[(6.23±1.48)μmol/mg vs.(10.65±2.14)μmol/mg,t=0.873,P＜0.05].The GPX4 and SOD levels in the tumor tissue of the iron death inhibition group were higher than those of the honokiol group[(10.12±2.15)mU/mg,(12.57±1.96)U/mg vs.(4.62±1.76)mU/mg,(7.05±2.09)U/mg,t=0.751,0.765,P＜0.05];The MDA level in the tumor tissue of the iron death activation group was higher than that of the honokiol group[(9.56±2.01)μmol/mg vs.(4.32±1.79)μmol/mg,t=0.521,P＜0.05].The GPX4 and SOD lev-els in the tumor tissue of the iron death activation group were lower than those of the honokiol group[(5.71±1.28)mU/mg,(7.27±1.92)U/mg vs.(9.05±1.53)mU/mg,(11.29±1.64)U/mg,t=0.823,0.737,P＜0.05].The p-YAP1/YAP1 ratio in the Houpo phenol group was lower than that in the control group[(10.25±2.04)μg/L vs.(18.71±1.86)μg/L,t=1.536,P＜0.05];The p-YAP1/YAP1 ratio in the iron death inhibition group was higher than that in the honokiol group[(15.17±1.26)µg/L vs.(6.52±2.30)µg/L,t=1.237,P＜0.05],while the p-YAP1/YAP1 ratio in the iron death activation group was lower than that in the honokiol group[(7.61±1.85)µg/L vs.(16.54±2.06)µg/L,t=1.037,P＜0.05].Conclusion Houpo phenol can induce ferroptosis in gastric cancer mice and has anti-cancer effects,which may be related to the inhibition of YAP elements.
HonokiolGastric cancerFerroptosisYes-associated protein 1
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