| 周邓婧,宋启斌,李 娜.Erastin联合顺铂诱导顺铂耐药鼻咽癌细胞发生铁死亡[J].肿瘤学杂志,2021,27(11):900-904. |
| Erastin联合顺铂诱导顺铂耐药鼻咽癌细胞发生铁死亡 |
| Erastin Combined with Cisplatin Induce Ferroptosis in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells |
| 投稿时间：2021-08-12 |
| DOI：10.11735/j.issn.1671-170X.2021.11.B002 |
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| 中文关键词: 鼻咽癌 铁死亡 耐药 Erastin 顺铂 |
| 英文关键词:nasopharyngeal carcinoma ferroptosis chemoresistance erastin cisplatin |
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| 中文摘要: |
| 摘 要：［目的］ 探究铁死亡激活剂Erastin联合顺铂（cisplatin，DDP）能否诱导鼻咽癌顺铂耐药细胞发生铁死亡。［方法］ CCK-8法检测鼻咽癌普通细胞株HNE-1、CEN2Z、HONE-1和顺铂耐药株HNE-1/DDP对DDP以及Erastin的敏感性，CCK-8法测定Erastin、DDP联合处理后HNE-1/DDP细胞活性变化，流式细胞学检测细胞死亡及细胞活性氧（reactive oxygen species，ROS）水平，Fe2+和丙二醛（malondialdehyde，MDA）试剂盒检测细胞Fe2+水平和MDA水平，Western blot检测铁死亡相关蛋白表达。［结果］ HNE-1/DDP对DDP的敏感度远低于正常HNE-1细胞系，Erastin的IC50高达（45.89±6.89） μmol/L。流式细胞学结果显示Erastin或DDP单独处理HNE-1/DDP时，死亡率不超过30%，ROS水平增高不超过15%。Erastin联合DDP能使HNE-1/DDP细胞死亡率提高至89.69%±9.48%，ROS水平提高至18.72%±3.05%。联合处理还提高了细胞内Fe2+和MDA水平，降低了铁死亡相关蛋白谷胱甘肽过氧化物酶4（recombinant glutathione peroxidase 4，GPX4）的表达，且铁死亡抑制剂Ferrostatin-1能逆转Erastin联合DDP所诱导的细胞死亡，抑制ROS、Fe2+以及MDA水平的增高。［结论］ Erastin联合DDP能通过降低GPX4表达诱导顺铂耐药株HNE-1/DDP铁死亡。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the effect of erastin combined with cisplatin（DDP) on ferroptosis in cisplatin-resistant nasopharyngeal carcinoma cells. ［Methods］ CCK-8 method was used to detect the sensitivity of nasopharyngeal carcinoma HNE-1， CEN2Z， HONE-1 cells and cisplatin-resistant HNE-1/DDP cells to cisplatin and erastin. HNE-1/DDP cells were treated with erastin and DDP. The cell death rate and reactive oxygen species（ROS) level of HNE-1/DDP was determined by flow cytometry. The intracellular Fe2+ level was assessed using an iron colorimetric assay kit， The levels of malondialdehyde（MDA) were detected with an MDA assay kit. Western blot was used to access the expression of ferroptosis-related protein GPX4. ［Results］ HNE-1/DDP cell was less sensitive to DDP or erastin， compared with other nasopharyngeal carcinoma cells. The IC50 of erastin was（45.89±6.89） μmol/L， and it was significantly decreased to（17.56±4.07） μmol/L after treatment with DDP and erastin（P<0.05). Flow cytometry showed that the death rate of HNE-1/DDP cells treated by erastin or DDP alone was less than 30%， and the ROS level was less than 15%. However， the death rate was increased to 89.69%±9.48% after treatment with erastin and DDP， and the ROS level increased to 18.72%±3.05%（P<0.05). The combined treatment also increased intracellular Fe2+ and MDA levels， decreased the expression of ferroptosis related protein GPX4， and all of these could be reversed by ferroptosis inhibitor ferrostatin-1. ［Conclusion］ Erastin combined with cisplatin can significantly induce the ferroptosis of cisplatin-resistant nasopharyngeal carcinoma HNE-1/DDP cells by reducing the expression of ferroptosis-related protein GPX4. |
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