Simvastatin, an HMG-CoA reductase inhibitor, exhibits antimetastatic and antitumorigenic effects in endometrial cancer

Abstract

OBJECTIVE-Our goal was to evaluate the effects of simvastatin on endometrial cancer cell lines and primary cultures of endometrial cancer cells.METHODS-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.RESULTS-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. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases

“…The analysis of qRT-PCR showed improved wounds healing as a result of simvastatin treatment due to inhibition of AKT/mTOR and the effects of simvastatin on inflammatory process (Rezvanian et al 2021 ). Simvastatin suppressed endometrial cancer cells (ECC) proliferation in a dose dependent way due to inhibition of the AKT/mTOR pathway in ECC and Ishikawa cells (Table 2 ) (Stine et al 2014 ). RCC is often resistant to chemotherapy and radiation.…”