Lipophilic Statins inhibit growth and invasiveness of human endometrial cells

Statins may be potential medication to decrease proliferation and invasiveness of endometrial cells

Key Points

Highlights:

• Lipophilic statins, namely simvastatin, has been observed to decrease invasiveness and proliferation of healthy endometrial stromal cells.

Key results:

• Human endometrial stromal (HES) cells that were administered with simvastatin were found to proliferate 47-89% less than controls, in a concentration-dependent manner.
• Cell viability testing revealed that administration of all lipid-soluble statins decreased the number of viable cells.
• An increase in caspase activity was seen when HES cells were treated with increasing doses of simvastatin. Pravastatin had no significant effect on caspase activity at any of the tested concentrations.
• Invasiveness of HES cells significantly decreased when treated with all lipid-soluble statins, depending on the specific statin administered.

What’s done here?

• The effect of multiple lipid and water-soluble statins on the growth of human endometrial stromal (HES) cells were compared.

Limitations:

• Effect of statin on HES cells were examined on healthy women and thus it is difficult to directly compare the results to those of endometriotic cells.

Lay Summary

Endometriosis is a disease process whereby cells of the endometrium grow and invade structures outside of the uterus. Through recent research, it has been seen that endometriotic foci in women with endometriosis exhibit an altered phenotype that contributes to its invasiveness and abnormal proliferation. Thus, understanding the interaction of potential medications to slow or halt the progression of endometriosis would allow for more targeted therapies to be developed.

Statins are a class of HMG-CoA reductase inhibitors widely used today as a cholesterol-lowering medication. Recently, research has found that statins are anti-inflammatory and inhibit enzymes involved in extracellular matrix remodeling which has been seen to be aberrant in endometriosis.

A team of researchers has recently published their findings on the effect of varying statins on endometrial cells in a paper titled “Lipophilic statins inhibit growth and reduce the invasiveness of human endometrial stromal cells” published in the Journal of Assisted Reproduction and Genetics.

The study first enrolled five healthy volunteers with no known endometriosis and through biopsies of the endometrium during the proliferative phase of the menstrual cycle, human endometrial stromal (HES) cells were then isolated and cultured. Data was then collected in the absence and presence of multiple lipid-soluble statins (simvastatin, lovastatin, and atorvastatin) and a water-soluble statin (pravastatin). Using various laboratory techniques, these HES cells were evaluated for the effect of statins on DNA synthesis, cell viability, and activity of caspases 3/7 (otherwise known as executioner caspases due to their role in cellular apoptosis or programmed cell death) and invasiveness.

Results from the cell proliferation assay revealed that while all lipid-soluble statins (simvastatin, lovastatin, and atorvastatin) significantly decreased the number of proliferating HES cells, simvastatin had the greatest effect; decreasing cell proliferation depending on the concentration.

Pravastatin decreased cell proliferation minimally. Mirroring these results, cell viability testing revealed that administration of all lipid-soluble statins decreased the number of viable cells. Caspase 3/7 activity was used as a marker for apoptosis and was found to be significantly increased when simvastatin, lovastatin, and atorvastatin were used. The greatest increase in caspase 3/7 activity was seen when HES cells were treated with simvastatin. Pravastatin had no significant effect at any of the tested concentrations.

Invasiveness of HES cells significantly decreased when treated with all lipid-soluble statins.

The difference in the effectiveness between lipophilic and water-soluble statins was postulated to be partly due to their varying ability to enter cells since lipophilic statins can passively diffuse into cells while pravastatin had limited ability to enter HES cells.

While these results are promising, further study is required to confirm these results investigating endometriotic cells.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30554393