Reverse effect of curcumin on CDDP-induced drug-resistance via Keap1/p62-Nrf2 signaling in A549/CDDP cell
Asian Pacific Journal of Tropical Medicine
;
(12): 1190-1196, 2017.
Artigo
em Inglês
| WPRIM
| ID: wpr-819396
ABSTRACT
OBJECTIVE@#To assess the effect of curcumin on CDDP-induced drug resistance and explore the underlying molecular mechanism through Nrf2 system and autophagy pathway.@*METHODS@#A drug-resistant cell model was established by exposing A549/CDDP cell to 2 μg/mL CDDP. A549/CDDP cell was treated with 20 μg/mL CDDP and 10 μM curcumin. The cell viability and apoptosis level, the signals of Keap1/P62-Nrf2 and autophagy pathway were analyzed.@*RESULTS@#CDDP induction promoted drug-resistant phenotype in A549/CDDP cell and activated autophagy as well as Nrf2 signals in A549/CDDP cell. Meanwhile, curcumin combination attenuated autophagy and Nrf2 activation induced by CDDP, and reversed the drug-resistant phenotype. Notably, curcumin combination augmented Keap1 transcription. Furthermore, Keap1 ablation with short hairpin RNAs hampered the efficacy of curcumin, suggesting Keap1 played a crucial role on reversal effect of curcumin.@*CONCLUSIONS@#The present findings demonstrate that CDDP promotes abnormal activation of Nrf2 pathway and autophagy, leading to drug resistance of A549/CDDP cell. Curcumin attenuates this process and combat drug-resistance through its potent activation on Keap1 transcription, which is essential for interplay between oxidative stress induced Nrf2 activation and autophagy/apoptosis switch.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Asian Pacific Journal of Tropical Medicine
Ano de publicação:
2017
Tipo de documento:
Artigo
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