RT Journal Article
SR Electronic
T1 FDX1 expression promotes DSF/Cu-induced cuproptosis in gastric cancer cells
JF Cancer Biology & Medicine
JO Cancer Biology & Medicine
FD China Anti-Cancer Association
SP 20250323
DO 10.20892/j.issn.2095-3941.2025.0323
A1 Li, Qirong
A1 Guo, Yi
A1 Yuan, Jiahuan
A1 Feng, Qiang
A1 Zhou, Hengzong
A1 Hao, Ming
A1 Tao, Boqiang
A1 Sun, Liqun
A1 Lin, Chao
A1 Mu, Jianfeng
A1 Guo, Gongliang
A1 Wang, Dongxu
YR 2026
UL http://www.cancerbiomed.org/content/early/2026/07/28/j.issn.2095-3941.2025.0323.abstract
AB Objective: Gastric cancer (GC) is a prevalent malignant tumor that warrants the development of drugs and therapeutic targets. Cuproptosis has emerged as a promising mechanism by which to inhibit tumors because copper homeostasis disorders frequently occur in various malignancies. The combination of disulfiram (DSF) and copper ions (DSF/Cu) has been shown to have significant antitumor effects. This study utilized DSF/Cu to investigate the mechanism underlying cuproptosis in GC cells.Methods: GC cells were treated with DSF/Cu and protein sequencing was performed to screen for differentially expressed genes. The mechanism by which overexpressed FDX1 regulates cuproptosis and WDR43 expression was determined. Subsequently, how to improve the efficacy of DSF/Cu in the treatment of GC was studied in a mouse model of GC.Results: DSF/Cu had a good therapeutic effect on promoting cuproptosis in GC cells. Protein sequencing revealed WDR43 as a downstream gene of FDX1. Increasing the expression of FDX1 enhanced the sensitivity of GC cells to copper treatment and inhibited the expression of WDR43, thereby exerting an antitumor effect. Furthermore, DSF/Cu was loaded into exosomes derived from natural killer (NK) cells to enhance the biological safety and tumor targeting of DSF/Cu and validate the inhibitory effect on GC both in vitro and in vivo.Conclusions: This study showed that DSF/Cu promoted cuproptosis and the expression of FDX1 affected cuproptosis sensitivity of GC. Moreover, the combination of NK cell exosomes with DSF/Cu improved the therapeutic effect of DSF/Cu, which helps to promote the targeted therapy of GC and improve clinical applicability.The data generated in this study are available upon request to the corresponding author.