河北医学2025，Vol.31Issue(5)：736-743,8.DOI:10.3969/j.issn.1006-6233.2025.05.06
MAC30调控JNK/Nrf2/HO-1介导的铁死亡促进乳腺癌细胞凋亡
MAC30 Regulating Ferroptosis Mediated by JNK/Nrf2/HO-1 Pathway to Promote Apoptosis in Breast Cancer Cells
摘要
Abstract
Objective:To investigate the effect of MAC30 on breast cancer cell apoptosis through the regulation of ferroptosis mediated by JNK/Nrf2/HO-1 pathway.Methods:The mRNA and protein expression levels of MAC30 were detected in normal breast cells and various breast cancer cell lines.MCF-7 cells were divided into four groups:the control group,the NC-shRNA group(MCF-7 cells transfected with MAC30-NC-shRNA),the MAC30-shRNA group(MCF-7 cells transfected with MAC30-shRNA),and the MAC30-shRNA+SP600125 group(MCF-7 cells transfected with MAC30-shRNA and treated with JNK inhibitor).RT-qPCR and Western blot were used to detect the mRNA and protein expression levels of MAC30 in each group of MCF-7 cells to verify the transfection efficiency.CCK-8 assay,clone formation experiment,and flow cy-tometry were used to detect cell viability,clone number,and apoptosis in each group.Kits were utilized to measure the levels of ROS,MDA,GSH,and Fe2+within cells of each group.RT-qPCR and Western blot were conducted to detect the mRNA and protein expression levels of iron death-related genes(GPX4,SLC7A11)in cells of each group.Western blot was also used to detect the expression levels of apoptosis-re-lated proteins(Caspase-3,Bax,Bcl-2)and proteins related to the JNK/Nrf2/HO-1 signaling pathway(JNK,p-JNK,Nrf2,HO-1)in cells of each group.Results:Compared to the control group and the NC-shRNA group,the MAC30-shRNA group exhibited decreased mRNA and protein expression levels of MAC30,cell viability,and clone number in MCF-7 cells(P<0.05).Additionally,the apoptosis rate of MCF-7 cells,expression levels of Caspase-3 protein and Bax/Bcl-2,mRNA and protein expression levels of ferropto-sis-related genes,as well as the expression levels of p-JNK/JNK and Nrf2(cytoplasmic)were increased(P<0.05).Conversely,the expression levels of Nrf2(nuclear)and HO-1 were decreased(P<0.05).Com-pared to the MAC30-shRNA group,the MAC30-shRNA+SP600125 group exhibited increased levels of MAC30 mRNA and protein expression,cell viability,and clone number within MCF-7 cells(P<0.05).Ad-ditionally,there were decreases in the apoptosis rate,Caspase-3 protein levels,Bax/Bcl-2 expression ratios,mRNA and protein expression levels of ferroptosis-related genes,and expression levels of p-JNK/JNK and Nrf2(cytoplasmic)(P<0.05).Conversely,the expression levels of Nrf2(nuclear)and HO-1 increased(P<0.05).Conclusion:Knockdown of MAC30 may promote apoptosis in breast cancer cells by regulating iron death mediated through the JNK/Nrf2/HO-1 signaling pathway.关键词
MAC30/乳腺癌/JNK/Nrf2/HO-1信号通路/铁死亡/凋亡Key words
MAC30/Breast cancer/JNK/Nrf2/HO-1 signaling pathway/Ferroptosis/Ap-optosis引用本文复制引用
罗永升,索岳尔,梁伟萍,陶冶..MAC30调控JNK/Nrf2/HO-1介导的铁死亡促进乳腺癌细胞凋亡[J].河北医学,2025,31(5):736-743,8.基金项目
吉林省青年发展基金,(编号:JDYY102020012) （编号:JDYY102020012）
