Celastrol induces apoptosis of gastric cancer cells by miR-21 inhibiting PI3K/Akt-NF-κB signaling pathway.
Pharmacology
; 93(1-2): 39-46, 2014.
Article
em En
| MEDLINE
| ID: mdl-24434352
ABSTRACT
OBJECTIVE:
Celastrol, a plant triterpene, has anticancer effects by increase of apoptosis. In the present study, the mechanism of celastrol on gastric cancer cell apoptosis was examined.METHODS:
The effect of celastrol on PI3K/Akt and the NF-κB signaling pathway was evaluated with Western blot and luciferase reporter assay. miR-21 expression was determined using real-time PCR. miR-21 inhibitor and miR-21 mimic were used to downregulate and upregulate miR-21 expression, respectively.RESULTS:
It was identified that celastrol was capable of inducing apoptosis of gastric cancer cells, which was mediated via inhibiting the activation of PI3K/Akt and NF-κB. A strong activator of Akt, IGF-1 restored NF-κB activity in cells treated with celastrol. Celastrol could also significantly suppress miR-21 expression. Furthermore, miR-21 inhibitor could decrease phospho-Akt expression and NF-κB activity. Notably, upregulation of miR-21 expression can increase PI3K/Akt and NF-κB activity and decrease apoptosis of gastric cancer cells treated with celastrol, which could be reversed by PI3K inhibitor.CONCLUSIONS:
Our data revealed that the effect of celastrol on apoptosis was due to miR-21 inhibiting the PI3K/Akt-dependent NF-κB pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Triterpenos
/
MicroRNAs
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article