Suppression of fumarate hydratase activity increases the efficacy of cisplatin-mediated chemotherapy in gastric cancer.
Cell Death Dis
; 10(6): 413, 2019 05 28.
Article
en En
| MEDLINE
| ID: mdl-31138787
ABSTRACT
Gastric cancer (GC) is one of the most common malignancies worldwide. Due to the low rate of early detection, most GC patients were diagnosed as advance stages and had poor response to chemotherapy. Some studies found that Fumarate hydratase (FH) participated in the DNA damage response and its deficiency was associated with tumorigenesis in some cancers. In this study, we investigated the relationship between FH and cisplatin (CDDP) sensitivity in GC cell lines. We found that FH was the most significant gene which induced by CDDP treatment and the suppression of FH could enhance the cytotoxicity of CDDP. Miconazole Nitrate (MN) could inhibit FH activity and enhance the effect of CDDP in vitro and in vivo. We also investigated the significance of expression of FH in GC tissues. The FH expression, which was higher in GC tissues than in noncancerous tissues, was negatively associated with the prognosis of patients. Together, these results revealed that FH is a reliable indicator for response to CDDP treatment in GC and the inhibition of FH may be a potential strategy to improve the effects of CDDP-based chemotherapy.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Cisplatino
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Resistencia a Antineoplásicos
/
Proliferación Celular
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Fumarato Hidratasa
Tipo de estudio:
Prognostic_studies
/
Screening_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2019
Tipo del documento:
Article