| 毛蕊异黄酮通过Nrf2/HO-1信号途径诱导人甲状腺癌FTC-133细胞发生铁死亡 |
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| 引用本文： | 谭 雄,陈 洁,熊国祚,申 昕,颜红霞.毛蕊异黄酮通过Nrf2/HO-1信号途径诱导人甲状腺癌FTC-133细胞发生铁死亡[J].现代肿瘤医学,2022,0(18):3269-3274. |
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| 作者姓名： | 谭 雄 陈 洁 熊国祚 申 昕 颜红霞 |
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| 作者单位： | 南华大学附属第二医院血管疝儿童普外科，湖南 衡阳 421001 |
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| 基金项目： | 湖南省卫健委科研项目（编号:B2019111） |
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| 摘 要： | 目的:观察毛蕊异黄酮（CA）是否可诱导人甲状腺癌细胞系FTC-133细胞铁死亡并探讨其可能机制。方法: 采用RPMI 1640培养液培养FTC-133细胞，分为对照和CA、铁死亡抑制剂ferrostatin-1、血红素氧合酶-1（HO-1）激动剂CoPP、CA+ferrostatin-1和CA+CoPP组。CCK-8法检测细胞增殖。相应试剂盒检测细胞活性氧（ROS）、还原型谷胱甘肽（GSH）、丙二醛（MDA）、总铁和二价铁离子水平。Western Blot检测细胞中谷胱甘肽过氧化物酶4（GPX4）、铁蛋白重链1（FTH1）、核因子E2相关因子2（Nrf2）和HO-1蛋白表达。结果:与对照组比较，CA（50、100和150 μmol/L）处理在24 h、48 h和72 h三个时间点均降低细胞存活率，并呈现剂量依赖性（均P＜0.05）。与对照组比较，CA（50、100和150 μmol/L）处理48 h降低细胞中GSH的浓度（均P＜0.05），增加了FTC-133细胞中ROS、MDA、总铁和二价铁离子浓度（均P＜0.05）。与对照组比较，CA（50、100和150 μmol/L）处理48 h显著降低细胞中GPX4（P＜0.05）和FTH1（P＜0.05）蛋白表达水平（均P＜0.05）。Ferrostatin-1部分逆转了CA诱导FTC-133细胞铁死亡的作用（均P＜0.05）。与对照组比较，CA（50、100和150 μmol/L）处理均降低Nrf2在细胞核中的表达及Nrf2在细胞核中表达与Nrf2总蛋白表达的比值（均P＜0.05），而没有影响Nrf2总蛋白表达（均P＞0.05）。与对照组比较，CA（50、100和150 μmol/L）处理均降低细胞中HO-1的蛋白表达（均P＜0.05）。CoPP部分逆转了CA诱导FTC-133细胞铁死亡的作用（均P＜0.05）。结论:CA诱导了人甲状腺癌细胞系FTC-133细胞发生铁死亡，而其机制可能是通过Nrf2/HO-1信号通路。
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| 关 键 词： | 毛蕊异黄酮 甲状腺癌 铁死亡 Nrf2/HO-1信号通路 |
Calycosin induces the ferroptosis in human thyroid cancer cell line FTC-133 cells through Nrf2/HO-1 signaling pathway |
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| TAN Xiong,CHEN Jie,XIONG Guozuo,SHEN Xin,YAN Hongxia.Calycosin induces the ferroptosis in human thyroid cancer cell line FTC-133 cells through Nrf2/HO-1 signaling pathway[J].Journal of Modern Oncology,2022,0(18):3269-3274. |
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| Authors: | TAN Xiong CHEN Jie XIONG Guozuo SHEN Xin YAN Hongxia |
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| Affiliation: | Department of Pediatric Surgery,the Second Affiliated Hospital,University of South China,Hunan Hengyang 421001，China. |
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| Abstract: | Objective:To investigate whether calycosin (CA) induces the ferroptosis in human thyroid cancer cell line FTC-133 cells and explore its possible mechanism.Methods:FTC-133 cells were cultured in RPMI 1640 medium.The experiment was divided into control group and CA group,ferroptosis inhibitor ferrostatin-1 group,heme oxygenase-1 (HO-1) agonist cobalt protoporphyrin (Copp) group,CA+ferrostatin-1 group and CA+Copp group.CCK-8 method was used to detect the cell proliferation.Reactive oxygen species (ROS),reduced glutathione (GSH),total iron and ferrous iron ion were detected by the kit.Western Blot was used to detect the protein expressions of glutathione peroxidase 4 (GPX4),ferritin heavy chain 1 (FTH1),nuclear factor erythroid-2-related factor 2 (Nrf2) and HO-1.Results:Compared with the control group,the cell survival rates were significantly reduced by CA (50,100 and 150 μmol/L) at 24,48 and 72 h in a dose-dependent manner (all P＜0.05).Compared with the control group,the concentrations of GSH were significantly decreased and the levels of ROS,MDA,total iron and ferrous iron ion (all P＜0.05) in FTC-133 cells were significantly increased by treatment with CA (50,100 and 150 μmol/L) for 48 h.Compared with the control group,the expression levels of GPX4 and FTH1 were significantly decreased by treatment with CA (50,100 and 150 μmol/L) for 48 h (all P＜0.05).Ferrostatin-1 partially reversed the effect of CA induced ferroptosis in FTC-133 cells (all P＜0.05).Compared with the control group,the expression of Nrf2 in the nucleus of FTC-133 and the ratio of Nrf2 expression in the nucleus to the total protein expression level of Nrf2 were significantly reduced by treatment with CA (50,100 and 150 μmol/L) for 48 h (all P＜0.05),without affecting the expressions of total protein of Nrf2 (all P＞0.05).Compared with the control group,the protein expression levels of HO-1 in FTC-133 cells were significantly down-regulated by treatment with CA (50,100 and 150 μmol/L) for 48 h (all P＜0.05).CoPP partially reversed the effect of CA on the ferroptosis of FTC-133 cells (all P＜0.05).Conclusion:CA induces the ferroptosis in human thyroid cancer cell line FTC-133 cells,and the mechanism may be through Nrf2/HO-1 signaling pathway. |
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| Keywords: | calycosin thyroid cancer ferroptosis Nrf2/HO-1 signaling pathway |
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