J Cancer 2021; 12(5):1386-1397. doi:10.7150/jca.52418 This issue

Research Paper

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

Ying Feng1, Fuyin Le1, Puyuan Tian2, Yanying Zhong1, Fuliang Zhan1, Genhua Huang1, Hui Hu1, Tingtao Chen1,2✉, Buzhen Tan1✉

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.

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Citation:
Feng Y, Le F, Tian P, Zhong Y, Zhan F, Huang G, Hu H, Chen T, Tan B. GTW inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer via ILK/AKT/GSK3β/Slug Signalling Pathway. J Cancer 2021; 12(5):1386-1397. doi:10.7150/jca.52418. Available from https://www.jcancer.org/v12p1386.htm

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Abstract

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