Objective To investigate the effect and mechanism of berberine(BBR)on apoptosis of triple negative breast cancer(TNBC)MDA-MB-231 cells.Methods The CCK-8 assay was used to evaluate the effect of BBR on the proliferative activity of MDA-MB-231 cells and calculate the IC50 values.Concentrations of 0,1/2 IC50,and IC50 were used for subsequent experiments.RT-PCR was performed to detect the mRNA expression levels of pro-apoptotic BAX and anti-apoptotic BCL2 in MDA-MB-231 cells after BBR treatment.Western blot was employed to analyze the protein expression levels of SIRT2,nuclear transcription factor NF-κB P65,acetylated P65,BAX,and BCL-2.Changes in mitochondrial membrane potential were assessed using a mitochondrial membrane potential detection assay.Results The CCK-8 assay revealed that BBR inhibited the proliferative activity of MDA-MB-231 cells(P＜0.05),with IC50 values of(92.282±12.297)μmol/L at 24 h and(54.544±6.092)μmol/L at 48 h.RT-PCR results showed that after BBR treatment,the mRNA expression level of BAX increased(P＜0.05),while that of BCL-2 decreased(P＜0.05)in MDA-MB-231 cells.Western blot analysis demonstrated that BBR reduced the protein expression level of silent information regulator 2(SIRT2)(P＜0.05),increased the protein expression of NF-κB P65(P＜0.05),and elevated the acetylation modification level of P65 as a substrate of SIRT2(P＜0.05).The expression of BAX increased(P＜0.05),while that of BCL-2 decreased(P＜0.05).The mitochondrial membrane potential decreased with increasing BBR concentrations(P＜0.05).Conclusion BBR can inhibit the growth of MDA-MB-231 cells.The mechanism may involve BBR's potential lysine deacetyltransferase(KDAC)inhibitor effect,suppressing the expression of SIRT2,altering the acetylation level of P65,and inducing mitochondrial pathway-related apoptosis in MDA-MB-231 cells.
berberinesirtuins 2nuclear factor kappa-Btriple negative breast cancerapoptosis
维普
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