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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2200405


Disulfiram enhances the antitumor activity of DDP by inhibiting the FA 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, Zhejiang University, Zijingang Campus, Hangzhou 310058, China; more

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

Key Words:  Disulfiram, DDP, DNA damage, 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 DDP by inhibiting the FA repair pathway[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .

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Abstract: 
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 the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, PI staining and western blot confirmed that the combination of DFS and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with GSEA pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: disulfiram 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 illustrates the potential mechanism of action of disulfiram in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

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