Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (1): 1-10.doi: 10.12092/j.issn.1009-2501.2025.01.001

Previous Articles     Next Articles

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

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

CLC Number: