• Home
  • Search Results
  • Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer.

Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer.

Gynecologic oncology (2014-06-01)
Monica N Schointuch, Timothy P Gilliam, Jessica E Stine, Xiaoyun Han, Chunxiao Zhou, Paola A Gehrig, Kenneth Kim, Victoria L Bae-Jump
ABSTRACT

Our goal was to evaluate the effects of simvastatin on endometrial cancer cell lines and primary cultures of endometrial cancer cells. Cell proliferation in the ECC-1 and Ishikawa endometrial cancer cell lines and primary cultures of endometrial cancer cells was assessed by MTT assay. Apoptosis and cell cycle were detected by Annexin V assay and propidium iodide staining, respectively. Reactive oxygen species and cell adhesion were assessed using ELISA assays. Invasion was analyzed using a transwell invasion assay. Mitochondrial DNA damage was confirmed using qPCR. The effects of simvastatin on the AKT/mTOR and MAPK pathways were determined by Western blotting. Simvastatin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines and 5/8 primary cultures of endometrial cancer cells. Simvastatin treatment resulted in G1 cell cycle arrest, a reduction in the enzymatic activity of HMG-CoA, induction of apoptosis as well as DNA damage and cellular stress. Treatment with simvastatin resulted in inhibition of the MAPK pathway and exhibited differential effects on the AKT/mTOR pathway in the ECC-1 and Ishikawa cells. Minimal change in AKT phosphorylation was seen in both cell lines. An increase in phosphorylated S6 was seen in ECC-1 and a decrease was seen in Ishikawa. Treatment with simvastatin reduced cell adhesion and invasion (p<0.01) in both cell lines. Simvastatin had significant anti-proliferative and anti-metastatic effects in endometrial cancer cells, possibly through modulation of the MAPK and AKT/mTOR pathways, suggesting that statins may be a promising treatment strategy for endometrial cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Simvastatin, ≥97% (HPLC), solid
Supelco
Simvastatin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
DL-3-Hydroxy-3-methylglutaryl coenzyme A sodium salt hydrate, ≥90% (HPLC)
Supelco
Simvastatin, analytical standard
USP
Simvastatin, United States Pharmacopeia (USP) Reference Standard
Simvastatin, European Pharmacopoeia (EP) Reference Standard