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小檗碱诱导骨肉瘤细胞铁死亡的作用及机制
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| 篇名： | 小檗碱诱导骨肉瘤细胞铁死亡的作用及机制 |
| TITLE： | Effect and mechanism of berberine-induced ferroptosis in osteosarcoma cells |
| 摘要： | 目的 探讨小檗碱对MG63骨肉瘤细胞铁死亡的影响及机制。方法以不加药的细胞为对照，用不同浓度（2.5、5.0、10.0μmol/L）小檗碱作用于细胞24h，检测细胞存活率、铁死亡相关指标[细胞核增殖相关抗原Ki-67（Ki67）、线粒体超微结构、Fe2+、活性氧（ROS）、丙二醛（MDA）和谷胱甘肽（GSH）]变化、信号转导及转录活化因子3（STAT3）与DNA结合活性以及磷酸化STAT3（p-STAT3）、肿瘤蛋白53（p53）和溶质载体家族7成员11（SLC7A11）蛋白表达水平。为观察p53在小檗碱诱导细胞铁死亡中的作用，转染p53siRNA，将细胞分为对照组、p53siRNA组、小檗碱组和p53siRNA+小檗碱组，以10.0μmol/L小檗碱作用24h后，检测细胞内p53和SLC7A11蛋白表达水平、线粒体膜电位、GSH水平以及MDA含量。为探究STAT3在小檗碱调控p53/SLC7A11信号通路中的作用，转染STAT3过表达质粒，将细胞分为对照组、小檗碱组、STAT3组和STAT3+小檗碱组，以10.0μmol/L小檗碱作用24h后，检测细胞内p-STAT3、STAT3、p53和SLC7A11蛋白表达水平。结果与对照细胞比较，2.5、5.0、10.0μmol/L小檗碱均能降低细胞存活率和细胞内Ki67蛋白表达，引起线粒体形态改变，升高细胞内Fe2+、ROS和MDA水平以及p53蛋白表达水平，降低GSH水平、STAT3与DNA的结合活性以及p-STAT3和SLC7A11蛋白表达水平，差异均有统计学意义（P＜0.05或P＜0.01）。与小檗碱组比较，p53siRNA+小檗碱组细胞内p53蛋白表达水平和MDA水平降低，SLC7A11蛋白表达水平、线粒体膜电位以及GSH水平升高，差异均有统计学意义（P＜0.01）。与小檗碱组比较，STAT3+小檗碱组细胞内p-STAT3、STAT3、SLC7A11蛋白表达水平升高，p53蛋白表达水平降低，差异均有统计学意义（P＜0.01）。结论小檗碱可通过STAT3/p53/SLC7A11信号通路诱导MG63细胞铁死亡。 |
| ABSTRACT： | OBJECTIVE To investigate the effect of berberine on ferroptosis in MG63 osteosarcoma cells and its mechanism. METHODS Using cells without drug treatment as control， the cell viability， proliferation， the related indexes of ferroptosis [nuclear proliferation associated-antigen （Ki67）， mitochondrial ultrastructure， ferric ion （Fe2+）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione （GSH）]， the protein expression of signal transducer and activator of transcription 3 （STAT3）， tumor protein 53 （p53）， and solute carrier family 7 member 11 （SLC7A11） were detected after being treated with different concentrations of berberine. Cells were transfected with p53 siRNA and then assigned to the control group， p53 siRNA group， berberine group， and p53 siRNA+berberine group to explore the role of p53 in berberine-induced ferroptosis. After 24 h incubation with 10.0 μmol/L berberine， the protein expressions of p53 and SLC7A11， the levels of mitochondrial membrane potential， GSH， and MDA content were determined. Cells were transfected with STAT3 overexpressed plasmid and then assigned to the control group， berberine group， STAT3 group， and STAT3+berberine group to explore the effect of STAT3 on the regulation of the p53/SLC7A11 pathway. After 24 h incubation with 10 μmol/L berberine， the protein expressions of p-STAT3， STAT3， p53， and SLC7A11 were detected. RESULTS Compared with the control cell， the concentrations of 2.5， 5.0 and 10.0 μmol/L berberine could reduce the cell viability and expression of Ki67， and induce the morphological changes in ferroptosis-related mitochondria， increase the levels of Fe2+， ROS and MDA， and the protein expression of p53， reduce the level of GSH， the binding activity of STAT3 with DNA， and the protein expressions of p-STAT3 and SLC7A11； the above differences were statistically significant （P＜ 0.05 or P＜0.01）. Compared with the berberine group，significantly down-regulated p53 protein expression and MDA level， up-regulated SLC7A11 protein expression， and increased mitochondrial membrane potential and GSH level were observed in the p53 siRNA+berberine group （P＜0.01）. Compared with the berberine group， the protein expressions of p-STAT3， STAT3， and SLC7A11 in the STAT3+berberine group were significantly increased （P＜0.01）， while the protein expression of p53 was significantly decreased （P＜0.01）. CONCLUSIONS Berberine can induce the ferroptosis of MG63 cells by mediating STAT3/p53/SLC7A11 signaling pathway. |
| 期刊： | 2024年第35卷第03期 |
| 作者： | 姬健钧；邱文奎 |
| AUTHORS： | JI Jianjun，QIU Wenkui |
| 关键字： | 小檗碱；铁死亡；骨肉瘤；信号转导及转录活化因子3；肿瘤蛋白53；溶质载体家族7成员11 |
| KEYWORDS： | berberine； ferroptosis； osteosarcoma； signal transducer and activator of transcription 3； tumor protein 53； solute |
| 阅读数： | 152 次 |
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