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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (1): 1-10.doi: 10.12092/j.issn.1009-2501.2025.01.001

• 基础研究 • 上一篇    下一篇

阿霉素/铜复合物诱导肝癌细胞发生铜死亡的机制研究

刘静1,2,雷国杰2,3,曹靖昊2,余灵艳2,杜璟2,王莹4   

  1. 1锦州医科大学研究生培养基地浙江省人民医院,杭州  310014,浙江;2浙江省人民医院(附属人民医院)检验中心,杭州医学院,杭州  310014,浙江;3浙江中医药大学,杭州  310053,浙江;4杭州市第一人民医院GCP机构办公室,杭州  310014,浙江

  • 收稿日期:2024-01-03 修回日期:2024-07-30 出版日期:2025-01-26 发布日期:2025-01-02
  • 通讯作者: 王莹,女,博士,研究员,博士生导师,研究方向:临床药理学、肿瘤药理学和神经药理学。 E-mail:nancywangying@163.com
  • 作者简介:刘静,女,硕士,研究方向:肿瘤药理学。 E-mail:Katrilx1225@163.com
  • 基金资助:
    国家自然科学基金资助项目(82102938)

Mechanism of doxorubicin/copper complex induced cuproptosis in hepatocellular carcinoma cells

LIU Jing1,2, LEI Guojie2,3, CAO Jinghao2, YU Lingyan2, DU Jing2, WANG Ying4   

  1. 1 Jinzhou Medical University Graduate Training Base of Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China; 2 Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Laboratory Center, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China; 3 Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China;  4 Office of GCP, Hangzhou First People's Hospital, Hangzhou 310014, Zhejiang, China
  • Received:2024-01-03 Revised:2024-07-30 Online:2025-01-26 Published:2025-01-02

摘要:

目的:探究阿霉素/铜(DOX/Cu)复合物诱导肝癌细胞铜死亡的作用机制。方法:采用DOX/Cu 0、2.5、4、7.5、10和12.5 μmol/L处理人肝癌细胞株Huh7,CCK-8法检测细胞活力,激光共聚焦显微镜和增殖试剂盒观察细胞增殖水平,细胞划痕实验测定细胞侵袭能力,流式细胞术检测细胞内活性氧(ROS)和铜离子水平,Western blot检测出细胞内铁硫簇蛋白表达水平。结果:随着DOX/Cu浓度的升高,细胞活力、细胞增殖能力和侵袭能力逐渐下降。铜离子螯合剂(TTM)能显著恢复DOX/Cu对细胞活力的影响。DOX/Cu处理细胞后,铜死亡相关指标细胞内铜离子和ROS水平显著升高,并伴随着铁硫簇蛋白的丢失。结论:DOX/Cu可通过铜死亡的方式抑制肝癌细胞。

关键词: 阿霉素, 铜, 肝癌, 铜死亡

Abstract:

AIM: To explore the mechanism of doxorubicin/copper (DOX/Cu) complex induced copper death in hepatocellular carcinoma cells. METHODS: Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0, 2.5, 4, 7.5, 10 and 12.5 μmol/L. The cell viability was detected by CCK-8 method. The cell proliferation level was observed by laser microscopy and proliferation kit. The cell invasion ability was determined by cell scratch assay. The flow cytometry was used to detect intracellular reactive oxygen species (ROS) and copper ion levels. And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels. RESULTS: With the increase of DOX/Cu concentration, cell viability, cell proliferation and invasion ability decreased gradually. The copper ion chelating agent (TTM) can significantly restore the effects of DOX/Cu on cell viability. After DOX/Cu treatment, intracellular copper ion and ROS levels related to coproptosis were significantly increased, accompanied by the loss of iron-sulfur cluster proteins. CONCLUSION: DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

Key words: doxorubicin, copper, hepatocellular carcinoma, cuproptosis

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