AURKA激活JAK2/STAT3通路抑制铁死亡促进神经胶质瘤细胞替莫唑胺耐药OA
AURKA promotes Temozolomide resistance in glioma cells by inhibiting ferroptosis through activation of the JAK2/STAT3 pathway
目的 探讨Aurora激酶A(AURKA)对神经胶质瘤细胞替莫唑胺(TMZ)耐药的影响及其对铁死亡的调控作用.方法 通过GEPIA2 数据库挖掘AURKA在胶质瘤中的表达谱及其与预后的相关性.建立U87MG/TMZ和LN229/TMZ耐药细胞株,利用qRT-PCR和Western blot检测AURKA的mRNA和蛋白表达.通过siRNA沉默AURKA,采用BODIPY-C11 染色、FerroOrange铁探针及免疫荧光技术,动态监测脂质过氧化水平、胞内铁含量及谷胱甘肽过氧化物酶 4(GPX4)表达.通过CCK-8 法评估细胞活力及半数抑制浓度(IC50),TUNEL染色检测细胞凋亡.利用STAT3 激活剂处理细胞,Western blot检测JAK2/STAT3 通路活性,并评估AURKA与铁死亡调控的分子关联.结果 AURKA在胶质瘤组织中高表达,与患者不良预后显著相关.U87MG/TMZ和LN229/TMZ耐药细胞中AURKA表达水平显著升高.沉默AURKA后,U87MG/TMZ和LN229/TMZ细胞中脂质过氧化产物及游离铁水平升高,GPX4 蛋白表达下调.铁死亡抑制剂可部分逆转AURKA敲低导致的细胞活力和TMZ耐药下降.AURKA沉默显著抑制JAK2/STAT3 通路活化,外源性激活STAT3可部分恢复细胞存活率,并削弱AURKA敲低对铁死亡的促进作用.结论 AURKA通过激活JAK2/STAT3 通路抑制铁死亡,从而增强神经胶质瘤细胞对TMZ的耐药性.
Objective To investigate the impact of Aurora kinase A(AURKA)on Temozolomide(TMZ)resistance in glioma cells and its regulatory role in ferroptosis.Methods The expression profile of AURKA in glioma and its correlation with prognosis were explored using the GEPIA2 database.U87MG/TMZ and LN229/TMZ drug-resistant cell lines were established,and the mRNA and protein expression levels of AURKA were detected by qRT-PCR and Western blot,respectively.AURKA was silenced using siRNA,and dynamic monitoring of lipid peroxidation levels,intracellular iron content,and glutathione peroxidase 4(GPX4)expression was conducted using BODIPY-C11 staining,FerroOrange iron probe,and immunofluorescence,respectively.Cell viability and IC50 were assessed by the CCK-8 assay,and cell apoptosis was detected by TUNEL staining.Following STAT3 activator treatment,JAK2/STAT3 pathway activity was detected by Western blot,and the molecular association between AURKA and ferroptosis regulation was evaluated.Results AURKA was highly expressed in glioma tissues,which was significantly associated with poor prognosis of patients.AURKA expression was significantly upregulated in U87MG/TMZ and LN229/TMZ resistant cells compared to parental cells.After AURKA silencing,lipid peroxidation products and free iron levels increased,while GPX4 protein expression decreased in U87MG/TMZ and LN229/TMZ cells.Ferroptosis inhibitor partially reversed the decrease in cell viability and TMZ resistance induced by AURKA knockdown.AURKA silencing significantly inhibited JAK2/STAT3 pathway activation;exogenous activation of STAT3(Colivelin)partially restored cell viability and attenuated the promotion of ferroptosis by AURKA knockdown.Conclusion AURKA enhances TMZ resistance in glioma cells by inhibiting ferroptosis through the activation of the JAK2/STAT3 pathway.
邹荣基;喻芳芳;刘腾飞;李丹霞;张俊斌;贾卓鹏
西安医学院第一附属医院神经外科(西安 710077)西安医学院第一附属医院神经内科(西安 710077)西安医学院第一附属医院神经外科(西安 710077)西安医学院第一附属医院神经外科(西安 710077)西安医学院第一附属医院神经外科(西安 710077)西安医学院第一附属医院神经外科(西安 710077)
医药卫生
神经胶质瘤细胞Aurora激酶A铁死亡JAK2/STAT3替莫唑胺耐药
Glioma cellsAURKAFerroptosisJAK2/STAT3Temozolomide resistance
《医学新知》 2026 (1)
70-79,10
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