KPT-330 and Y219 exert a synergistic antitumor effect in triple-negative breast cancer through inhibiting NF-κB signaling.
FEBS Open Bio
; 13(4): 751-762, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36847599
ABSTRACT
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype, which has poor prognosis due to the lack of effective targeted drugs. KPT-330, an inhibitor of the nuclear export protein CRM-1, has been widely used in clinical medicine. Y219, a novel proteasome inhibitor designed by our group, shows superior efficacy, reduced toxicity, and reduced off-target effects as compared to the proteasome inhibitor bortezomib. In this study, we investigated the synergistic effect of KPT-330 and Y219 against TNBC cells, as well as the underlying mechanisms. We report that combination treatment with KPT-330 and Y219 synergistically inhibited the viability of TNBC cells in vitro and in vivo. Further analysis revealed that the combined use of KPT-330 and Y219 induced G2-M phase arrest and apoptosis in TNBC cells, and attenuated nuclear factor kappa B (NF-κB) signaling by facilitating nuclear localization of IκB-α. Collectively, these results suggest that the combined use of KPT-330 and Y219 may be an effective therapeutic strategy for the treatment of TNBC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
FN-kappa B
/
Neoplasias de la Mama Triple Negativas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
FEBS Open Bio
Año:
2023
Tipo del documento:
Article
País de afiliación:
China