Elesclomol combined with Cu2 + induced cuproptosis in hepatoma cell lines PLC/PRF/5 and Huh-7
10.19405/j.cnki.issn1000-1492.2025.08.015
- VernacularTitle:伊利司莫 －铜离子诱导肝癌细胞系 PLC/PRF/5 和 Huh⁃7 发生铜死亡
- Author:
Qiaohui Ren
1
;
Xinyue Zhu
1
;
Wei Lv
1
;
Yan Zang
1
;
Lianzi Wang
1
;
Xinyi Zhou
1
;
Junxiao Yao
1
;
Tao Li
1
Author Information
1. Dept of Clinical Laboratory, The First Afiliated Hospital of Anhui Medical University, Hefei 230022
- Publication Type:Journal Article
- Keywords:
total glycosides of paeony;
glucocorticoid;
dexamethasone;
liver injury;
oxidative stress;
endoplasmic reticulum stress
- From:
Acta Universitatis Medicinalis Anhui
2025;60(8):1470-1477
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis.
Methods: Human hepatoma cell lines PLC/PRF/5 and Huh_7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating agent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh_7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK_8 kit. The cell death induced by ES + Cu2 + was detected by flow cytometry and the changes of ES + Cu2 + after pretreatment with copper chelating agent ATTM. The expression of Cuproptosis related proteins ATPase copper transporting beta (ATP7B) ,ferredoxin 1 (FDX1) , dihydrolipoamide s_acetyltransferase(DLAT) and superoxide dismutase 1 (SOD1) were detected by Western blot. The effect of ES + Cu2 + on cell proliferation and the reverse effect after ATTM pretreatment was detected by cell scratch assay.
Results:The toxicity of ES + Cu2 + to human hepatocellular carcinoma cell lines PLC/PRF/5 and Huh_7 was significantly dose_dependent (P < 0. 05) . Compared with the control group , the combined application of ES and Cu2 + had a more significant inhibitory effect on hepatocellular carcinoma cells than ES or Cu2 + alone (P < 0. 05) , and copper chelating agent ATTM could reverse the inhibitory effect of ES + Cu2 + on hepatocellular carcinoma cells (P < 0. 05) . Flow cytometry results showed that compared with the control group , the proportion of cell death in PLC/PRF/5 and Huh_7 cells treated with ES + Cu2 + increased , while the proportion of cell death decreased after ATTM intervention (P < 0. 05) . The results of cell scratch test showed that the migration ability of PLC/PRF/5 and Huh_7 cells was decreased after ES + Cu2 + treatment , however, the addition of ATTM reversed the inhibitory effect of ES + Cu2 + on cell migration (P < 0. 05) . Compared with the control group , the expression levels of copper death related proteins ATP7B , FDX1 , DLAT and SOD1 decreased after ES + Cu2 + treatment , but the addition of ATTM reversed the expression trend of these proteins (P < 0. 05) .
Conclusion:The combination of ES and Cu2 + can effectively inhibit the proliferation and migration of PLC/PRF/5 and Huh_7 of hepatocellular carcinoma cells , and induce Cuproptosis , which provides a new strategy for the treatment of hepatocellular carcinoma.
- Full text:202604050041451216伊利司莫-铜离子诱导肝癌细胞系PLC_PRF_5和Huh-7发生铜死亡_任俏慧.pdf
