Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of WWOX on epithelial-mesenchymal transition in ovarian cancer cells in vivo, and its association with Elf5/Snail-1 signal pathway

Chunhuan Song¹, Yuchen Yan², Yongli Liu¹, Lisha Fang³, Qiang Li⁴, Yang Xu³, Hongchao Yan^3.4

¹Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou 221008; ²The First Clinical School of Xuzhou Medical University, Xuzhou 221004; ³Department of Obstetrics and Gynecology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000; ⁴Xuzhou Medical University Science Park Development Co., Ltd, Xuzhou 221000, China.

For correspondence:- Hongchao Yan Email: hneb26@163.com

Accepted: 29 June 2021 Published: 29 July 2021

Citation: Song C, Yan Y, Liu Y, Fang L, Li Q, Xu Y, et al. Effect of WWOX on epithelial-mesenchymal transition in ovarian cancer cells in vivo, and its association with Elf5/Snail-1 signal pathway. Trop J Pharm Res 2021; 20(7):1411-1417 doi: 10.4314/tjpr.v20i7.13

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate how WW domain-containing oxidoreductase (WWOX) gene affects epithelial-mesenchymal transition (EMT) of ovarian cancer (OC) cells, and the implication of Elf5/Snail-1 pathway in the process.

Methods: This study employed female BALB/c nude mice aged 6 weeks. The expression levels of E-cadherin, β-Catenin, N-cadherin, Vimentin, Snail1 and Elf5 were assayed using qRT-PCR. The protein levels of WW1, WW2, E-cad, β-Cat, N-cad, vimentin, Snail-1 and Elf5 were determined using western blotting (WB). Invasion changes in cells in each group were analyzed by Transwell invasion test while WWOX and Elf5 were evaluated by GST pull-down test; furthermore, WWOX and ELF5 were evaluated by co-immunoprecipitation (COIP).

Results: Relative to control group, tumor volume and weight of WWOX high-expression mice were significantly decreased, while those of WWOX low-expression group were increased (p < 0.05). The levels of E-cad, Elf5 and β-catenin increased, but those of N-cad, Snail-1 and vimentin decreased in WWOX high expression group. In the WWOX low-expression group, the levels of E-cad, Elf5 and β-cat were down-regulated, while those of N-cad, Snail-1 and vimentin were up-regulated (p < 0.05). The expression of E-cad, Elf5 and β-cat declined; on the other hand, those of N-Cad, Snail-1 and vimentin were elevated after mutation of WW1 domain in WWOX gene (p < 0.05).

Conclusion: Based on the in vivo results, the role of WWOX/Elf5/Snail1 signal route in the epithelial-mesenchymal transition of ovarian cancer, and its related mechanisms have been clarified. This provides a new target for gene therapy of ovarian cancer.

Keywords: WWOX gene, Elf5, Snail1, Ovarian cancer, BALB/c nude mice