Actinidia chinensis Planch prevents proliferation and migration of gastric cancer associated with apoptosis, ferroptosis activation and mesenchymal phenotype suppression - 19/04/20
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Highlights |
• | Actinidia chinensis Planch(ACP) suppresses proliferation and migration of gastric cancer cells. |
• | ACP treatment elevated the apoptosis and ferroptosis but suppressed mesenchymal phenotype in HGC-27 cells. |
• | ACP suppressed tumor growth in the zebrafish xenograft model. |
Abstract |
Actinidia chinensis Planch (ACP) was the kiwifruit plant Chinese kiwifruit Actinidia chinensis Planch Root, which had been approved to be an anti-tumor drug widespread in clinical. However, the specific mechanism of ACP in resistance to gastric cancer remained unclear. Therefore, our study was dedicated to investigate the anti-proliferation and anti-migration effects of ACP on gastric cancer cells and its molecular mechanisms. Firstly, we utilized HPLC-MS to analyze the composition of ACP decoction, the results showed that ACP contained two main anti-tumor components, Ursolic acid and Oleanolic acid. The proliferation and migration ability of HGC-27 were examined by CCK-8 and cell scratch tests respectively. In addition, we also investigated HGC-27 cells apoptosis, mesenchymal phenotype and ferroptosis after ACP rat drug-containing serum (ACPs) treatment. EGFP-expressing lentiviral vectors were utilized to construct HGC-27 cells which containing green fluorescence. Then we take advantages of containing green fluorescence cells to establish a zebrafish xenograft model in vivo. The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.
Le texte complet de cet article est disponible en PDF.Abbreviations : ACP, EMT, GPx4, Fer-1, GC, TMN, PBS, DAPI
Keywords : Gastric cancer, Actinidia chinensis Planch, Apoptosis, Ferroptosis, Mesenchymal phenotype
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