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J Assist Reprod Genet. 2018 Dec 15. doi: 10.1007/s10815-018-1352-9. [Epub ahead of print]

Lipophilic statins inhibit growth and reduce invasiveness of human endometrial stromal cells.

Author information

1
Department of Obstetrics and Gynecology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
2
Department of Obstetrics and Gynecology, University of California Davis, 4860 Y Street, Sacramento, CA, 95817, USA.
3
Department of Psychiatry, University of California Riverside, 900 University Ave., Riverside, CA, 92521, USA.
4
Division of Reproductive Endocrinology and Infertility, Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0633, USA. aduleba@ucsd.edu.

Abstract

PURPOSE:

To compare effects of lipid-soluble statins (simvastatin, lovastatin, atorvastatin) and water-soluble statin (pravastatin) on growth and invasiveness of human endometrial stromal (HES) cells.

METHODS:

Endometrial biopsies were collected during the proliferative phase from five volunteers. HES cells were isolated and cultured in the absence or in the presence of simvastatin, lovastatin, atorvastatin, and pravastatin. Effects of statins on DNA synthesis, cell viability, activity of caspases 3/7 and invasiveness were evaluated.

RESULTS:

The proliferation of HES cells was significantly decreased by simvastatin (by 47-89%), lovastatin (by 46-78%), and atorvastatin (by 21-48%) in a concentration-dependent manner. Activity of executioner caspases 3/7 was significantly increased by simvastatin (by 10-25%), lovastatin (by 19%) and atorvastatin (by 7-10%) in a concentration-dependent manner. The greatest effects were observed in response to simvastatin. Accounting for the effects of statins on cell number, the invasiveness of HES cells was significantly decreased in cells treated with simvastatin (by 49%), lovastatin (by 54%), and atorvastatin (by 53%). Pravastatin had little or no effects on any of the tested endpoints.

CONCLUSIONS:

Present findings demonstrate that only lipid-soluble among tested statins were effective in inhibition of growth and invasiveness of HES cells. These findings may have clinical relevance in treatment of endometriosis.

KEYWORDS:

Endometrial stroma; Endometriosis; Hydrophilic; Lipophilic; Statins

PMID:
30554393
DOI:
10.1007/s10815-018-1352-9

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