Effects of resveratrol on proliferation and apoptosis in rat ovarian theca-interstitial cells.

Effects of resveratrol on proliferation and apoptosis in rat ovarian theca-interstitial cells.
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DOI:
10.1093/molehr/gaq002
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发表时间:
2010-04
影响因子:
4
通讯作者:
Donna H. Wong;J. Villanueva;Amanda B. Cress;A. Duleba
Donna H. Wong;J. Villanueva;Amanda B. Cress;A. Duleba
中科院分区:
医学2区
文献类型:
--
作者:
Donna H. Wong;J. Villanueva;Amanda B. Cress;A. Duleba

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多囊卵巢综合征(PCOS)以卵巢功能障碍为特征,与卵巢膜间质(T-I)细胞增生、高胰岛素血症、全身性炎症和氧化应激相关。这项体外研究测试了白藜芦醇是否可以改变有或没有胰岛素的大鼠T-I细胞生长,白藜芦醇是一种具有抗癌,抗炎,抗增殖和抗氧化特性的天然多酚。大鼠T-I细胞培养与白藜芦醇和/或胰岛素,和DNA合成的影响,活细胞数和凋亡的标志物进行了评估。白藜芦醇单独诱导一个有效的浓度依赖性抑制细胞生长,抑制DNA合成,减少活细胞的数量和增加的活动的刽子手半胱天冬酶3和7;白藜芦醇的这些影响抵消了促增殖和抗凋亡的胰岛素的作用。白藜芦醇孵育的细胞的免疫荧光分析显示,浓度和时间依赖性的形态学变化与凋亡一致。目前的研究结果表明,白藜芦醇促进细胞凋亡,减少大鼠T-I细胞在体外的生长,以及抑制胰岛素诱导的大鼠T-I细胞的生长。这表明白藜芦醇和/或介导其作用的机制可能与PCOS的新治疗方法的开发有关,PCOS的特征在于过度的卵巢间充质生长和高胰岛素血症。
Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and associated with ovarian theca-interstitial (T-I) cell hyperplasia, hyperinsulinemia, systemic inflammation and oxidative stress. This in vitro study tested whether rat T-I cell growth with or without insulin can be altered by resveratrol, a natural polyphenol with anti-carcinogenic, anti-inflammatory, anti-proliferative and antioxidant properties. Rat T-I cells were cultured with and without resveratrol and/or insulin, and the effects on DNA synthesis, number of viable cells and markers of apoptosis were evaluated. Resveratrol alone induced a potent concentration-dependent inhibition of cell growth by inhibiting DNA synthesis, decreasing the number of viable cells and increasing the activity of executioner caspases 3 and 7; these effects of resveratrol counteracted the pro-proliferative and anti-apoptotic effects of insulin. Immunofluorescence analysis of cells incubated with resveratrol showed concentration- and time-dependent morphological changes consistent with apoptosis. The present findings indicate that resveratrol promotes apoptosis to reduce rat T-I cell growth in vitro as well as inhibiting insulin-induced rat T-I cell growth. This suggests a possibility that resveratrol and/or mechanisms mediating its effect may be relevant to the development of novel treatments for PCOS, which is characterized by both excessive ovarian mesenchyma growth and hyperinsulinemia.