Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation

Yao,Shujuan; Wang,Wen; Zhou,Bin; Cui,Xiujuan; Yang,Hui; Zhang,Shiqian

doi:10.3892/etm.2021.10826

Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation

Authors:
- Shujuan Yao
- Wen Wang
- Bin Zhou
- Xiujuan Cui
- Hui Yang
- Shiqian Zhang
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Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Obstetrics and Gynecology, Jining Medical University Affiliated Tengzhou Central People's Hospital, Tengzhou, Shandong 277599, P.R. China, Department of Obstetrics and Gynecology, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China
Published online on: September 30, 2021 https://doi.org/10.3892/etm.2021.10826
Article Number: 1390
Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is the most lethal gynecologic malignancy, and is usually diagnosed at an advanced stage. Most patients relapse within 12-24 months and die from progressive chemotherapy-resistant diseases. Significant progress has been made in developing new targeted therapies for human cancer, including ovarian cancer. However, an effective alternative to drug development is to repurpose drugs. The present study investigated the possibility of reusing the antibiotic monensin as an anti-ovarian cancer drug. After applying a series of titrated monensin on a panel of ovarian cancer cell lines, the growth, migration and invasion of cells were explored. Multiple signaling molecules associated with epithelial-to-mesenchymal transition were also regulated by monensin. The mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway was further found to be the key regulator affected by monensin. Additionally, monensin enhanced the MEK1 SUMOylation in vitro and in vivo, and the SUMOylation degree depended on time and dose. Xenograft studies verified that monensin effectively inhibited xenograft tumor growth by increasing the SUMOylation of MEK1. The aforementioned results suggested that monensin is a good candidate for anti-ovarian cancer by enhancing MEK1 SUMOylation and inhibiting the MEK-ERK pathway.

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