Effects of honokiol on epithelial mesenchymal transformation of breast cancer cells
Objective To investigate the effect of honokiol on epithelial mesenchymal transformation(EMT)in breast cancer and its mechanism.Methods MDA-MB-231 cells were randomly divided into control group(normal culture),low dose group(40 µmol·L-1 honokiol),middle dose group(50 μmol·L-honokiol),high dose group(60 μmol·L-1 honokiol),si-NC group(transfected with si-NC),si-NF2 group(transfected with si-NF2),DMSO group(treated with dimethyl sulfoxide)and verteporfin group(12 μmol·L-1 Verteporfin,hippo pathway inhibitor).The cell survival rate of each group was detected by methyl thiazolyl tetrozolium(MTT)assay;Transwell assay detected cell migration in each group;Western blot assay was used to detect the expression of EMT-related protein.BALB/c female mice were randomly divided into model group(construct transplanted tumor model),experimental-L group(give 100 mg·kg-1 and honokiol after modeling)and experimental-H group(give 200 mg·kg-1 and honokiol after modeling),with 10 mice in each group.Tumor volume and weight were detected after treatment;Western blot assay was used to detect the expression of EMT-related proteins.Results The cell survival rates of control group,low dose group,middle dose group and high dose group were(100.00±4.02)％,(80.14±6.51)％,(64.05±6.21)％and(53.70±5.19)％;the migration number of cells were 276.30±14.77,219.40±12.50,162.20±9.53 and 100.10±6.50;the relative expression levels of neurofibrin 2(NF2)protein were 0.52±0.04,0.60±0.06,0.65±0.07 and 0.78±0.10;the relative expression levels of programmed cell death ligand 1(PD-L1)protein were 0.70±0.06,0.47±0.04,0.41±0.05 and 0.36±0.03,respectively.The above indexes in low,middle and high dose groups were significantly different from those in control group(all P＜0.05).The tumor volume of model group,experimental-L group and experimental-H group were(922.02±109.61),(743.04±64.04)and(605.00±72.63)mm3;the tumor weight were(0.87±0.10),(0.66±0.10)and(0.53±0.11)g;the relative expression levels of PD-L1 protein were 0.74±0.08,0.51±0.05 and 0.42±0.05;the relative expression levels of N-cadherin protein were 0.75±0.07,0.60±0.10 and 0.51±0.04,respectively.The above indexes in the experimental-L,-H groups were significantly different from those in the model group(all P＜0.05).Conclusion Honokiol may inhibit EMT in breast cancer cells by regulating NF2-hippo signaling pathway in PD-L1.
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