GTW inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer via ILK/AKT/GSK3ß/Slug Signalling Pathway.
J Cancer
; 12(5): 1386-1397, 2021.
Article
em En
| MEDLINE
| ID: mdl-33531984
ABSTRACT
Background:
Epithelial ovarian cancer (EOC) accounts for the most lethal of all gynaecological cancers which is attributed to metastasis, invasiveness and drug resistance. A crucial link has been found between epithelial-mesenchymal transition (EMT) and cancer metastasis and chemo-resistance. Previous studies have confirmed that one of the main components of tripterygium glycosides (GTW)-triptolide (TPL) has anticancer effects.Methods:
The purpose of this study is to determine whether GTW could inhibit EMT in A2780/DPP cells in vitro and in vivo, and explore the underlying mechanism.Results:
In vitro results showed that GTW inhibited cell proliferation, invasion and migration, and intensified the sensitivity of A2780/DDP cells to cisplatin (DDP). GTW, especially GTW+DDP, significantly inhibited the expression of N-cadherin, integrin-linked kinase (ILK), phospho-protein kinase B/AKT (PKB/p-AKT), phospho-glycogen synthase kinase (p-GSK3ß) and Slug, while it increased E-cadherin levels by inhibiting EMT via the ILK/AKT/GSK3ß/Slug signalling pathway. Animal results indicated that GTW, especially GTW+DDP, significantly reduced tumour burden, prolonged the life span of mice, and down-regulated the levels of tumour markers CA125 and HE4 by regulating EMT through the ILK/AKT/GSK3ß/Slug signalling pathway.Conclusion:
Our results highlighted the significance of EMT in EOC metastasis, invasiveness and resistance to DDP and investigated the potential role of GTW as an adjuvant therapeutic agent in chemo-resistant EOC.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Cancer
Ano de publicação:
2021
Tipo de documento:
Article