南京中医药大学学报2026，Vol.42Issue(5)：689-698,10.DOI:10.14148/j.issn.1672-0482.2026.0689
冬凌草甲素通过PINK1/Parkin通路诱导三阴性乳腺癌发生线粒体自噬的机制研究
Mechanism of Oridonin Inducing Mitophagy in Triple Negative Breast Cancer Through PINK1/Parkin Pathway
摘要
Abstract
OBJECTIVE To explore the effect of Oridonin(Ori)on proliferation,apoptosis and mitophagy of triple negative breast cancer(TNBC)and its specific mechanism.METHODS CCK8 method was used to explore the effect of Ori on the activity of triple negative breast cancer MDA-MB-231 cells and determine the concentration of drugs that can effectively inhibit the growth of tu-mor cells.The effects of Ori on apoptosis and Reactive Oxygen Species(ROS)were detected by flow cytometry.Western blot was used to detect the expression of cell apoptosis-related proteins Caspase-9,Bax and mitophagy-related proteins LC3B,p62,PINK1 and Par-kin.MDC staining was used to observe whether autophagy occurred in MDA-MB-231 cells after drug intervention;immunofluores-cence was used to detect the expression of LC3B,PINK1 and Parkin proteins in cells and their co-location with mitochondria.The ef-fects of Ori on proliferation and autophagy of TNBC were verified by subcutaneous transplantation of tumor animals.RESULTS Ori could significantly inhibit the activity of TNBC cells,and the IC50 was 20.57 µmol·L-1.At the same time,Ori could significantly pro-mote cell apoptosis(P<0.001)and increase ROS content in cells(P<0.05),up-regulate the expression of cell apoptosis-related pro-teins Bax(P<0.01),and up-regulated the expression of activated Caspase-9 protein(P<0.01).In addition,Ori could promote au-tophagy in TNBC cells,up-regulate the expression of autophagy-related proteins LC3B Ⅱ/Ⅰ and p62(P<0.05,P<0.001),and up-regulated the expression of mitophagy-related proteins PINK1 and Parkin(P<0.01)and their co-localization with mitochondria..The animal experiment of subcutaneous transplanted tumor confirmed that compared with the control group,the high-dose Ori group could significantly inhibit tumor growth and promote mitophagy of tumor cells.CONCLUSION Ori induces mitophagy in triple negative breast cancer through PINK1/Parkin pathway,which inhibits tumor growth.关键词
冬凌草甲素/三阴性乳腺癌/凋亡/自噬/线粒体自噬/PINK1/Parkin/LC3BKey words
oridonin/triple negative breast cancer/apoptosis/autophagy/mitophagy/PINK1/Parkin/LC3B分类
医药卫生引用本文复制引用
姚丹,祁玉麟,郭煜君,陈念芝..冬凌草甲素通过PINK1/Parkin通路诱导三阴性乳腺癌发生线粒体自噬的机制研究[J].南京中医药大学学报,2026,42(5):689-698,10.基金项目
中国博士后科学基金项目(2023MD734135) （2023MD734135）
重庆市博士后科学基金项目(CSTB2023NSCQ-BHX0019) （CSTB2023NSCQ-BHX0019）
