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2014 ; 134
(2
): 346-55
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Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and
anti-tumorigenic effects in endometrial cancer
#MMPMID24880141
Schointuch MN
; Gilliam TP
; Stine JE
; Han X
; Zhou C
; Gehrig PA
; Kim K
; Bae-Jump VL
Gynecol Oncol
2014[Aug]; 134
(2
): 346-55
PMID24880141
show ga
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. CONCLUSION: 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.