Oncotarget

Research Papers:

Simvastatin is a potential candidate drug in ovarian clear cell carcinomas

Nicolai Skovbjerg Arildsen and Ingrid Hedenfalk _

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Oncotarget. 2020; 11:3660-3674. https://doi.org/10.18632/oncotarget.27747

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Abstract

Nicolai Skovbjerg Arildsen1,2 and Ingrid Hedenfalk1

1 Division of Oncology, Department of Clinical Sciences, Lund and Lund University Cancer Center, Lund University, Lund, Sweden

2 Current Address: Leo Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Correspondence to:

Ingrid Hedenfalk,email: Ingrid.Hedenfalk@med.lu.se

Keywords: ovarian clear cell cancer; simvastatin; CID-1067700; Rho GTPase; actin

Received: May 27, 2020     Accepted: September 01, 2020     Published: October 06, 2020

Copyright: © 2020 Arildsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Ovarian clear cell carcinomas (OCCC) constitute a rare subtype of epithelial ovarian cancer, lacking efficient treatment options. Based on previous studies, we assessed the anti-proliferative effect of simvastatin, a Rho GTPase interfering drug, in three OCCC cell lines: JHOC-5, OVMANA and TOV-21G, and one high-grade serous ovarian cancer (HGSOC) cell line, Caov3. We used the Rho GTPase interfering drug CID-1067700 as a control. All OCCC cell lines were more sensitive to single-agent simvastatin than the HGSOC cells, while all cell lines were less sensitive to CID-1067700 than to simvastatin. Combinations of carboplatin and simvastatin were generally antagonistic. Most treatments inhibited migration, while only simvastatin and CID-1067700 also disrupted actin organization in the OCCC cell lines. All treatments induced a G1 arrest in JHOC-5 and TOV-21G cells. Treatments with simvastatin consistently reduced c-Myc protein expression in all OCCC cell lines and displayed evidence of causing both caspase-mediated apoptotic cell death and autophagic response in a cell line dependent manner. Differences between cell lines in response to the treatments were observed and such differences, including e. g. prior treatment, should be investigated further. Conclusively, simvastatin efficiently controlled OCCC proliferation and migration, thus showing potential as a candidate drug for the treatment of OCCC.


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