Department of Obstetrics and Gynecology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Department of Obstetrics and Gynecology, University of California Davis, 4860 Y Street, Sacramento, CA, 95817, USA.
J Assist Reprod Genet. 2019 Mar;36(3):535-541. doi: 10.1007/s10815-018-1352-9. Epub 2018 Dec 15.
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.
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.
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.
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.
比较脂溶性他汀类药物（辛伐他汀、洛伐他汀、阿托伐他汀）和水溶性他汀类药物（普伐他汀）对人子宫内膜基质（HES）细胞生长和侵袭的影响。
在增殖期从五名志愿者中采集子宫内膜活检。分离并培养 HES 细胞，使其在不存在或存在辛伐他汀、洛伐他汀、阿托伐他汀和普伐他汀的情况下生长。评估他汀类药物对 DNA 合成、细胞活力、半胱天冬酶 3/7 活性和侵袭性的影响。
HES 细胞的增殖被辛伐他汀（47-89%）、洛伐他汀（46-78%）和阿托伐他汀（21-48%）浓度依赖性地显著降低。执行器半胱天冬酶 3/7 的活性被辛伐他汀（10-25%）、洛伐他汀（19%）和阿托伐他汀（7-10%）浓度依赖性地显著增加。观察到最大的作用是对辛伐他汀的反应。考虑到他汀类药物对细胞数量的影响，用辛伐他汀（49%）、洛伐他汀（54%）和阿托伐他汀（53%）处理的 HES 细胞的侵袭性显著降低。普伐他汀对任何测试终点几乎没有或没有影响。
目前的研究结果表明，在所测试的他汀类药物中，只有脂溶性他汀类药物对 HES 细胞的生长和侵袭具有抑制作用。这些发现可能对子宫内膜异位症的治疗具有临床意义。
