GTW inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer via ILK/AKT/GSK3β/Slug Signalling Pathway

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-GSK3 beta) and Slug, while it increased E-cadherin levels by inhibiting EMT via the ILK/AKT/GSK3 beta/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/GSK3 beta/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.

Automated summary

The study found that tripterygium glycosides (GTW) can inhibit the proliferation, invasion, and migration of epithelial ovarian cancer cells by suppressing the EMT pathway. Animal experiments demonstrated that GTW can reduce tumor burden, prolong lifespan, and down-regulate levels of tumor markers by regulating the EMT pathway. The results suggest that GTW could be a potential adjuvant therapeutic agent for chemo-resistant epithelial ovarian cancer.