NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1ß/Wnt/ß-catenin signaling pathway.
Biosci Rep
; 40(7)2020 07 31.
Article
en En
| MEDLINE
| ID: mdl-32578856
ABSTRACT
BACKGROUND:
Gemcitabine is widely used in the treatment of breast cancer (BC). However, the resistance to drugs remains a tough concern. The study explored the potential mechanism concerning gemcitabine resistance in triple-negative BC (TNBC) in vitro.METHODS:
TNBC cells (TNBCC) and gemcitabine-resistance cell lines (GRC) were used. We investigated the sensitivity to gemcitabine responsive to regulation of Nod-like receptor protein 3 (NLRP3) expression in TNBCC in different gemcitabine concentrations. RT-PCR checked NLRP3 mRNA expression and MTT assessed the cell cytotoxicity. Gemcitabine resistance was studied in GRC exposed to 0, 1, 3, 5 nm gemcitabine after GRC were treated with NLRP3 agonist Nigericin sodium salt (NSS) or antagonist CY-09. Epithelial-to-mesenchymal transition (EMT) biomarkers were evaluated via RT-PCR and inflammasome IL-1ß, ß-catenin content and GSK-3ß activity were measured by ELISA methods. Last, we inactivated the signaling and examined the NLRP3, EMT mRNA expression by RT-PCR, IL-1ß, ß-catenin content and GSK-3ß activity by ELISA and cell cytotoxicity through MTT.RESULTS:
NLRP3 up-regulation improved cell survival and reduced sensitivity to gemcitabine (P<0.05). NLRP3 had higher expression in GRC than TNBCC. GRC cell viability dropped as the gemcitabine concentration increased. NLRP3 up-regulation added to resistance to gemcitabine in GRC (P<0.05). NLRP3 agonist might induce EMT process, activate wnt/ß-catenin signaling and IL-1ß, while inactivation of wnt/ß-catenin signaling could result in the inhibition of NLRP3, IL-1ß and EMT as well as cell viability in GRC (P<0.05).CONCLUSION:
NLRP3 could enhance resistance to gemcitabine via IL-1ß/EMT/Wnt/ß-catenin signaling, which suggested that NLRP3 antagonist CY-09 might be incorporated into gemcitabine treatment for TNBC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a Antineoplásicos
/
Desoxicitidina
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Neoplasias de la Mama Triple Negativas
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Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Female
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Humans
Idioma:
En
Revista:
Biosci Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
China