Simvastatin이 자궁내막증 환자의자궁내막 기질세포 증식과 세포자멸사에 미치는 영향
Effects of simvastatin on the proliferation and apoptosis of human endometrial stromal cells from women with endometriosis
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목적: 본 연구는 자궁내막증을 가진 여성의 자궁내막 기질세포 배양에 simvastatin을 첨가하여 세포증식 억제와 세포자멸사 유도에 미치는 영향을 알아보기 위하여 시행되었다. 연구 방법: 4명의 자궁내막증 환자로부터 채취한 자궁내막조직에서 분리한 자궁내막 기질세포를 simvastatin을 첨가하지 않은 대조군과 2 μM과 10 μM의 simvastatin을 각각 첨가한 처리군으로 나누어 48시간 배양한 후 세포의 형태를 관찰하고, 세포자멸사로 나타나는 sub-G1기를 측정하였다. 세포자멸사에 관여하는 유전자로 알려진 Bcl-2와 Bax의 발현 정도와 caspase-3 효소 활성도를 조사하였다결과: 대조군에 비해 simvastatin 농도가 높아짐에 따라 기질세포의 증식이 억제되었고, simvastatin 처리군에서 sub-G1기가 현저히 증가되어 simvastatin이 세포자멸사를 유도함을 알 수 있었다 (P<0.05). Bcl-2의 발현은 simvastatin을 처리한 군에서 대조군에 비해 감소하는 것으로 나타났으나 Bax의 발현에는 큰 변화가 없었다. Caspase-3의 효소 활성 조사에서 10 μM simvastatin을 첨가한 군이 대조군에 비해 활성도가 유의하게 증가하였다 (P<0.05). 결론: Simvastatin은 자궁내막 기질세포의 증식과 세포자멸사 억제유전자인 Bcl-2의 발현을 억제하고 caspase-3의 효소 활성을 증가시키는 것으로 나타나 자궁내막증의 치료제로 이용될 수 있을 것으로 사료된다.
Abstract
Objective: To evaluate the effects of simvastatin on the proliferation and apoptosis of human endometrial cells from women with endometriosis. Methods: Endometrial tissues were obtained from four women with endometriosis. The endometrial stromal cells isolated from tissue were cultured with 0, 2 and 10 μM simvastatin treatments for 48 hours. The proliferation of endometrial stromal cells was inhibited with 2 and 10 μM simvastatin treatments compared to control. The effect of simvastatin on the sub-G1 phase of cell cycle was determined by flow cytometry. The expression of apoptosis related molecule (Bcl-2, Bax and caspase-3) was examined in control and simvastatin treatments using western blot. Results: The sub-G1 phase was higher in 10 μM simvastatin than in control and 2 μM simvastatin (P<0.05). This result showed that simvastatin could induce apoptosis of stromal cells. The expression of Bcl-2 was increased in simvastatin treatments slightly (P<0.05) and the expression of Bax was not different between control and experimental groups. The activation of caspase-3 was significantly higher in 10 μM simvastatin treated group than control and 2 μM simvastatin treated groups (P<0.05). Conclusion: Simvastatin induces apoptosis of endometrial stromal cells and inhibits their proliferation. It was considered that simvastatin could potentially be a therapeutic agent for the treatment of endometriosis.
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