实用医学杂志 ›› 2023, Vol. 39 ›› Issue (10): 1206-1211.doi: 10.3969/j.issn.1006⁃5725.2023.10.003

• 基础研究 • 上一篇    下一篇

抑制血清素转运蛋白表达联合Erastin 诱导肠癌细胞铁死亡的实验研究 

杨金兰1 屈天银1 戴庆1 马晶晶2 喻皇飞1 李亚军1    

  1. 遵义医科大学第三附属医院(遵义市第一人民医院)1 肿瘤科,2 检验科(贵州遵义563000) 
  • 出版日期:2023-05-25 发布日期:2023-05-25
  • 通讯作者: 喻皇飞 E⁃mail:yhfei163@163.com;李亚军 E⁃mail: yajun790@163.com 杨金兰、屈天银为共同第一作者
  • 基金资助:
    国家自然科学基金项目(编号:81960506);贵州省基础研究(自然科学)项目(编号:黔科合基础[2019]1326 号);贵州省卫健委科学技术基金项目(编号:gzwkj2022⁃299) 

Ferroptotic cell death in colorectal cancer regulated by SERT inhibition combined with erastin 

YANG Jinlan*, QU Tianyin*,DAI Qing,MA Jingjing,YU Huangfei,LI Yajun.    

  1. Department of Oncology,the Third Affiliated Hos⁃ pital of Zunyi Medical University(the First People Hospital of Zunyi),Zunyi 563000,China 
  • Online:2023-05-25 Published:2023-05-25
  • Contact: YU Huangfei E⁃mail:yhfe163@163.com;LI Yajun E⁃mail:yajun790@163.com

摘要:

目的 观察肠癌 SW480 细胞经铁死亡诱导剂 Erastin 处理后血清素转运蛋白(serotonin transporter,SERT)表达的变化,探索调控 SERT 表达联合 Erastin 对肠癌细胞铁死亡的影响。方法 Erastin 处理肠癌 SW480 细胞,CCK8 检测细胞的存活能力,Western blot 评估细胞内血清素转运蛋白 SERT 及铁死 亡相关蛋白SLC7A11、GPX4和ACSL4的影响,流式细胞术分析癌细胞内ROS含量的变化。同时利用siRNA 干扰下调细胞内 SERT 表达,观察调节 SERT 表达联合 Erastin 对癌细胞铁死亡的影响。结果 10 μmol/L Erastin处理肠癌SW480细胞可诱导癌细胞发生铁死亡,并显著上调细胞中SERT表达。siSERT后Erastin所 致的癌细胞中铁死亡抵抗蛋白 SLC7A11 和 GPX4 下降更为显著,而铁死亡执行蛋白 ACSL4 则明显升高。 5⁃HT刺激不仅逆转Erastin对SW480细胞所致的SLC7A11和GPX4减少及铁死亡作用,同时还使得Erastin联 合siSERT对铁死亡的协同作用得到一定程度的抑制。结论 Erastin刺激在诱导肠癌SW480细胞发生铁死 亡的同时,代偿性上调了SERT的表达;抑制SERT表达可增加肠癌细胞对Erastin的铁死亡敏感性。 

关键词: 结直肠癌, 血清素转运蛋白, 5?羟色胺, 铁死亡

Abstract: Objective To observe the serotonin transporter (SERT) expression in colorectal cancer SW480 cells after treatment with erastin and investigate the effect of regulated SERT expression combined with erastin on ferroptosis in colorectal cancer cells. Methods The colorectal cancer SW480 cells were treated with erastin. CCK8 assay was used to verify cell viability,Western blot was used to evaluate the expression of SERT and ferroptosis related proteins such as SLC7A11,GPX4 and ACSL4,and flow cytometry was used to analyze the levels of ROS in the cancer cells. siRNA interference was used to down ⁃ regulate SERT expression in the SW480 cells and the effect of ferroptotic death in the cancer cells treated with regulated SERT combined with Erastin were observed. Results SW480 cells treated with 10 μmol erastin induced ferroptosis and significantly upregulated SERT expression in the cancer cells. The ferroptotic resistance proteins SLC7A11 and GPX4 in the cancer cells induced by erastin combined with siSERT were significantly reduced,while the ferroptotic executive protein ACSL4 was significantly increased. 5⁃HT stimulation not only reversed the reduction of SLC7A11 and GPX4 and ferroptosis caused by erastin on SW480 cells,but also inhibited the synergistic ferroptotic effect of erastin combined with siSERT. Conclusion Erastin induces ferroptotic cell death in SW480 cells and upregulates SERT expression in a compensatory way. Inhibited SERT can increase ferroptotic sensitivity of colorectal cancer cells to erastin. 

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