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Journal of Zhejiang University SCIENCE B

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Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway

Author(s):  Meng YUAN, Qian WU, Mingyang ZHANG, Minshan LAI, Wenbo CHEN, Jianfeng YANG, Li JIANG, Ji CAO

Affiliation(s):  Laboratory of Fruit Quality Biology / the State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Fruit Science Institute, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; more

Corresponding email(s):  caoji88@zju.edu.cn, jiangli49@zju.edu.cn

Key Words:  Disulfiram (DSF); Cisplatin (DDP); DNA damage; Fanconi anemia (FA) repair; Chemotherapy

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Meng YUAN, Qian WU, Mingyang ZHANG, Minshan LAI, Wenbo CHEN, Jianfeng YANG, Li JIANG, Ji CAO. Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway[J]. Journal of Zhejiang University Science B, 2023, 24(2): 207-220.

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author="Meng YUAN, Qian WU, Mingyang ZHANG, Minshan LAI, Wenbo CHEN, Jianfeng YANG, Li JIANG, Ji CAO",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway
%A Meng YUAN
%A Qian WU
%A Mingyang ZHANG
%A Minshan LAI
%A Wenbo CHEN
%A Jianfeng YANG
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 3
%P 207-220
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer

T1 - Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway
A1 - Meng YUAN
A1 - Qian WU
A1 - Mingyang ZHANG
A1 - Minshan LAI
A1 - Wenbo CHEN
A1 - Jianfeng YANG
A1 - Ji CAO
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 3
SP - 207
EP - 220
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.


1浙江大学农业与生物技术学院,果实品质生物实验室 / 农业部园艺作物生长发育与品质调实验室,中国杭州市,310058


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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