ACT001 reverses resistance of prolactinomas via AMPK-mediated EGR1 and mTOR pathways.
Endocr Relat Cancer
; 29(2): 33-46, 2021 12 13.
Article
en En
| MEDLINE
| ID: mdl-34821219
ABSTRACT
Dopamine agonist (DA) is the first choice for the treatment of prolactinomas, and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogs, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB resistance in GH3 cells by inhibiting the mTOR signaling pathway, inducing cell death through autophagy, and reverse the BRC resistance in MMQ cells by activating the EGR1 signaling pathway, inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Hipofisarias
/
Prolactinoma
/
Proteína 1 de la Respuesta de Crecimiento Precoz
/
Proteínas Quinasas Activadas por AMP
/
Serina-Treonina Quinasas TOR
/
Furanos
Límite:
Humans
Idioma:
En
Revista:
Endocr Relat Cancer
Asunto de la revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
Año:
2021
Tipo del documento:
Article
País de afiliación:
China