医学分子生物学杂志2025，Vol.22Issue(6)：571-578,8.DOI:10.3870/j.issn.1672-8009.2025.06.006
氧化槐果碱抑制Nrf2/HO-1/NQO1通路诱导乳腺癌细胞凋亡
Oxysophocarpine Induces Apoptosis of Breast Cancer Cells by Inhibi-tion of Nrf2/HO-1 Signaling Pathway
摘要
Abstract
Objective To investigate the effect of oxysophocarpine on breast cancer(BC)cell proliferation,apoptosis,and oxidative stress by modulating the nuclear factor erythroid 2-related fac-tor 2,(Nrf2)/heme oxygenase-1(HO-1)/NAD(P)H:quinone oxidoreductase 1(NQO1)pathway.Methods MDA-MB-231 and MCF-7 cell lines were used.Cell viability was detected by CCK-8 assay.Quantitative real-time polymerase chain reaction(qRT-PCR)or Western blotting were used to measure the expression level of proliferation-related(Survivin,Ki67,P21),apopto-sis-related(cleaved caspase-3/9,Bax/Bcl-2 ratio),and Nrf2/HO-1/NQO1 pathway-related mo-leculars.Apoptosis and mitochondrial membrane potential were analyzed by flow cytometry.Oxidative stress markers superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA))were assessed via enzyme-linked immunosorbent assay(ELISA).Nrf2 was overexpressed in MDA-MB-231 cells to validate the Nrf2/HO-1/NQO1 pathway's effect.A nude mouse xenograft model was established to evaluate tumor growth,Ki67 expression,caspase-3 positivity,apoptosis rate(TUNEL),and Nrf2/HO-1/NQO1 pathway protein expression levels.Results Oxysophocarpine inhibited BC cell viability,induced apoptosis,and reduced mitochondrial membrane potential in a dose-dependent manner.It significantly suppressed the expression of proliferation-related molecules(Survivin,Ki67),and promoted the expression of apoptosis-related molecules(P21,cleaved caspase-3/9,Bax/Bcl-2 ratio).Additionally,it inhibited Nrf2/HO-1/NQO1 pathway activation and exacerbated oxidative stress(reduced SOD,GSH;increased MDA).Nrf2 overexpression par-tially reversed these effects of oxysophocarpine.Animal experiments confirmed that oxysophocarpine inhibited tumor growth,reduced proliferation(Ki67),promoted apoptosis(caspase-3,TUNEL),and suppressed Nrf2 pathway activation in vivo.Conclusion Oxysophocarpine effective-ly inhibits breast cancer cell proliferation,induces apoptosis,and enhances oxidative stress by sup-pressing the Nrf2/HO-1/NQO1 signaling pathway.关键词
氧化槐果碱/乳腺癌/凋亡/氧化应激/Nrf2/HO-1/NQO1信号通路Key words
oxysophocarpine/breast cancer/apoptosis/oxidative stress/Nrf2/HO-1/NQO1 signaling pathway分类
医药卫生引用本文复制引用
崔敏,张彤,司梦圆,林莹,谢文杰,孙吉瑞..氧化槐果碱抑制Nrf2/HO-1/NQO1通路诱导乳腺癌细胞凋亡[J].医学分子生物学杂志,2025,22(6):571-578,8.基金项目
河北省2023年度医学科学研究课题计划(No.20232032) This work was supported by a grant from the Hebei Province 2023 Medical Science Research Project Plan(No.20232032) （No.20232032）
