[Wogonoside reverses cisplatin resistance in SGC7901/cDDP cells through inhibition of PI3K/Akt/Nrf2/ARE signaling pathway].
Sheng Li Xue Bao
; 70(4): 397-405, 2018 Aug 25.
Article
em Zh
| MEDLINE
| ID: mdl-30112565
ABSTRACT
The aim of this study was to investigate the effect of wogonoside (WGS) on the cisplatin (cDDP) resistance in human gastric carcinoma SGC7901/cDDP cells and its possible mechanism. The drug-resistant SGC7901/cDDP cells were established by stepwise exposure to cDDP. CCK-8 assay was employed to detect the cytotoxic effect of WGS and cDDP on SGC7901/cDDP cells, and the combined effect of WGS and cDDP was analyzed by Chou-Talalay method. Flow cytometry was used to determine the apoptosis and reactive oxygen species (ROS). Nuclear factor erythroid-2 related factor 2 (Nrf2) gene was knocked down by using the short hairpin RNA (shRNA) approach. The protein levels of Nrf2, NAD(P)Hquinone oxidoreductase 1 (NQO1), glutathione S transferase-π (GST-π), multidrug resistance-associated protein 1 (MRP1), cleaved Capase-3, p-Akt and Akt were detected by Western blotting. The result showed that after various concentrations of WGS and/or cDDP treatment for 48 h, the cell viability was remarkably reduced in a dose-dependent manner (P < 0.05). When the inhibition rate exceeded 16%, the combination of WGS and cDDP produced a synergistic effect. The protein levels of p-Akt, Nrf2 and MRP1 in SGC7901/cDDP cells were higher than those in SGC7901 cells (P < 0.05). WGS and LY294002 (PI3K inhibitor) both remarkably decreased the phosphorylation level of Akt (P < 0.05), down-regulated the protein level of Nrf2 (P < 0.05), increased the content of ROS (P < 0.05), up-regulated the protein level of cleaved Caspase-3 (P < 0.05), and induced apoptosis (P < 0.05). Meanwhile, N-acetyl-L-cysteine (NAC) decreased apoptosis and oxidative stress reaction induced by WGS (P < 0.05). WGS and Nrf2 gene silencing both down-regulated the protein levels of NQO1, GST-π and MRP1 (P < 0.05). These results suggest that WGS may reverse cDDP resistance in SGC7901/cDDP cells through blocking the PI3K/Akt/Nrf2/ARE signaling pathway, thus enhancing the cytotoxicity of cDDP and inducing oxidative stress reaction and apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Cisplatino
/
Resistencia a Medicamentos Antineoplásicos
/
Flavanonas
/
Glucosídeos
Limite:
Humans
Idioma:
Zh
Revista:
Sheng Li Xue Bao
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China