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Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B ; (12): 207-220, 2023.
Artículo en Inglés | WPRIM | ID: wpr-971481
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 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.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Síndrome de Abstinencia a Sustancias / Neoplasias Testiculares / Cisplatino / Apoptosis / Resistencia a Antineoplásicos / Línea Celular Tumoral / Proliferación Celular / Disulfiram / Alcoholismo / Anemia de Fanconi Límite: Femenino / Humanos / Masculino Idioma: Inglés Revista: Journal of Zhejiang University. Science. B Año: 2023 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Síndrome de Abstinencia a Sustancias / Neoplasias Testiculares / Cisplatino / Apoptosis / Resistencia a Antineoplásicos / Línea Celular Tumoral / Proliferación Celular / Disulfiram / Alcoholismo / Anemia de Fanconi Límite: Femenino / Humanos / Masculino Idioma: Inglés Revista: Journal of Zhejiang University. Science. B Año: 2023 Tipo del documento: Artículo