中国药理学通报2025，Vol.41Issue(5)：917-925,9.DOI:10.12360/CPB202408022
基于STAT3/GPX4/SLC7A11轴的新藤黄酸体内外诱导骨肉瘤铁死亡的作用和机制
Research on effect and mechanism of neogambogic acid induced ferroptosis in osteosarcoma in vitro and in vivo based on STAT3/GPX4/SLC7A11 axis
摘要
Abstract
Aim To investigate the effect of neogam-bogic acid(NGA)on inducing ferroptosis in osteosar-coma K7M2 cells and subcutaneous transplanted tumor mice and explore the underlying mechanism.Methods MTT assay was employed to detect the effect of NGA(1,2,4,8,16,32,64,128 μmol·L-1)on cell prolif-eration,and the IC50 value was calculated.Calcein AM assay was used to detect cell viability.Transwell was applied to detect cell invasion.TEM was utilized to ob-serve the mitochondria morphology.K7M2 cells were subjected to treat with ferroptosis inducers erastin(Era)and inhibitors ferrostatin-1(Fer-1)to assess the levels of MDA,GSH,Fe2+,and LDH.RT-qPCR and Western blot were used to detect the mRNA and protein expression of STAT3,GPX4,and SLC7A11.A transplanted tumor model was established and treated with NGA to assess the impact of it on tumor growth and ferroptosis in vivo.HE staining was applied to ana-lyze the pathological status of tumor tissues.Nile red fluorescence staining was applied to detect the level of lipid components in tumor tissues.Results The pro-liferation,viability and invasion ability of K7M2 cells were significantly reduced after treatment with NGA at different concentrations(P＜0.05),and typical fea-tures of ferroptosis such as decreased mitochondrial vol-ume and reduced mitochondrial spine were observed.Compared to the control,the expression of MDA,Fe2+and LDH significantly increased(P＜0.01),while the content of GSH significantly decreased(P＜0.01).The ferroptosis in osteosarcoma was enhanced by the erastin,while inhibited by ferrostatin-1.In terms of mechanism,NGA inhibited the mRNA and protein ex-pression levels of STAT3,GPX4 and SLC7A11(P＜0.05).In vivo experiments confirmed that NGA signif-icantly improved the pathological state of tumor tissues,inhibited tumor growth,and induced ferroptosis in os-teosarcoma tissue cells.Conclusion NGA induces ferroptosis in osteosarcoma cells both in vitro and in vi-vo by inhibiting the STAT3/GPX4/SLC7A11 signaling axis,thereby exerting an anti-osteosarcoma effect.关键词
新藤黄酸/骨肉瘤/STAT3/GPX4/SLC7A11轴/铁死亡/分子机制/脂质过氧化Key words
neogambogic acid/osteosarcoma/STAT3/GPX4/SLC7A11 axis/ferroptosis/molecular mecha-nism/lipid peroxidation分类
医药卫生引用本文复制引用
陈运动,李豫皖,赵海建,聂兴国,李中锋..基于STAT3/GPX4/SLC7A11轴的新藤黄酸体内外诱导骨肉瘤铁死亡的作用和机制[J].中国药理学通报,2025,41(5):917-925,9.基金项目
国家自然科学基金青年项目(No 82302853) （No 82302853）
