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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