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Simvastatin is a potential candidate drug in ovarian clear cell carcinomas

Arildsen, Nicolai Skovbjerg LU and Hedenfalk, Ingrid LU orcid (2020) In Oncotarget 11(40). p.3660-3674
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... (More)

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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Actin, CID-1067700, Ovarian clear cell cancer, Rho GTPase, Simvastatin
in
Oncotarget
volume
11
issue
40
pages
15 pages
publisher
Impact Journals
external identifiers
  • scopus:85094940961
ISSN
1949-2553
DOI
10.18632/ONCOTARGET.27747
language
English
LU publication?
yes
id
7593ed79-1a21-4f64-926e-17b0c6c8cb6f
date added to LUP
2020-11-17 08:56:01
date last changed
2022-04-19 02:08:49
@article{7593ed79-1a21-4f64-926e-17b0c6c8cb6f,
  abstract     = {{<p>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.</p>}},
  author       = {{Arildsen, Nicolai Skovbjerg and Hedenfalk, Ingrid}},
  issn         = {{1949-2553}},
  keywords     = {{Actin; CID-1067700; Ovarian clear cell cancer; Rho GTPase; Simvastatin}},
  language     = {{eng}},
  number       = {{40}},
  pages        = {{3660--3674}},
  publisher    = {{Impact Journals}},
  series       = {{Oncotarget}},
  title        = {{Simvastatin is a potential candidate drug in ovarian clear cell carcinomas}},
  url          = {{http://dx.doi.org/10.18632/ONCOTARGET.27747}},
  doi          = {{10.18632/ONCOTARGET.27747}},
  volume       = {{11}},
  year         = {{2020}},
}