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 cytometry 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-related 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 ferroptosis-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). Compared 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). Additionally, 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.
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): 736-742.
LUO Yongsheng, SUO Yueer, LIANG Weiping, et al. MAC30 Regulating Ferroptosis Mediated by JNK/Nrf2/HO-1 Pathway to Promote Apoptosis in Breast Cancer Cells. HeBei Med, 2025, 31(5): 736-742.
[1] Jatoi I,Kemp Z.Surgery for breast cancer prevention[J].JAMA,2021,325(17):1804. [2] Criscitiello C,Corti C.Breast cancer genetics:diagnostics and treatment[J].Genes,2022,13(9):1593. [3] 潘蕾蕾,马俊,叶亭亭,等.下调MAC30对乳腺癌细胞焦亡、血管生成及ATP1A2蛋白的作用机制[J].局解手术学杂志,2023,32(6):481-486. [4] Kwun MS,Lee GD.Ferroptosis-like death in microorganisms:a novel programmed cell death following lipid peroxidation[J].Microbiol Biotechnol,2023,33(8):992-997. [5] 阮芳,王云飞,王继水.基于JNK/p53通路探讨熊果酸诱导卵巢癌细胞系OVCAR3细胞铁死亡的作用及其机制[J].中华中医药学刊,2021,39(7):62-64,267. [6] Wei XN,Huang QQ,Chen JY,et al.Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway[J].Int Immunopath Ph,2023,37(12):54. [7] Lei S,Zheng R,Zhang S,et al.Global patterns of breast cancer incidence and mortality:a population-based cancer registry data analysis from 2000 to 2020[J].Cancer Commun,2021(41):1183-1194. [8] Zhang PF,Tian Q,Gao H,et al.Inhibition of MAC30 exerts antitumor effects in nasopharyngeal carcinoma via affecting the Akt/GSK-3β/β-catenin pathway[J].Biochem Mol Toxicol,2022,36(7):23061. [9] Bumbat M,Wang MX,Liang W,et al.Effects of Me2SO and trehalose on the cell viability,proliferation,and Bcl-2 family gene (BCL-2,BAX,and BAD) expression in cryopreserved human breast cancer cells[J].Biopreserv Biobank,2020,18(1):229-237. [10] Wang ZL,Yang L.Downregulation of ROR2 attenuates LPS-induced A549 cell injury through JNK and ERK signaling pathways[J].Immun Inflamm Dis,2023,11(4):803. [11] Yang J,Mo J,Dai J,et al.Cetuximab promotes RSL3-induced ferroptosis by suppressing the Nrf2/HO-1 signalling pathway in KRAS mutant colorectal cancer[J].Cell Death Dis,2021,12(11):1079-1111.
2025, Vol. 31 
冀公网安备13080202000786号