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

Ying Feng; Fuyin Le; Puyuan Tian; Yanying Zhong; Fuliang Zhan; Genhua Huang; Hui Hu; Tingtao Chen; Buzhen Tan

doi:10.7150/jca.52418

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

J Cancer. 2021 Jan 1;12(5):1386-1397. doi: 10.7150/jca.52418. eCollection 2021.

Authors

Ying Feng¹, Fuyin Le¹, Puyuan Tian², Yanying Zhong¹, Fuliang Zhan¹, Genhua Huang¹, Hui Hu¹, Tingtao Chen^{1

2}, Buzhen Tan¹

Affiliations

¹ Department of Obstetrics & Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
² Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, PR China.

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-GSK3β) and Slug, while it increased E-cadherin levels by inhibiting EMT via the ILK/AKT/GSK3β/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/GSK3β/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.

Keywords: A2780/DDP cells; Cisplatin (DDP) resistance; ILK/AKT/GSK3β/Slug pathway; Tripterygium glycosides (GTW); epithelial ovarian cancer (EOC); epithelial-mesenchymal transition (EMT).