EA-2160, MMS, Mer, Molecules, Sante, IUML: Institut Universitaire Mer et Littoral FR3473 CNRS, Faculty of Pharmacy, Nantes, France.
Anticancer Res. 2012 Jul;32(7):3007-13.
Liver X receptor (LXR) plays a key role in reverse cholesterol transport by inducing the expression of the ATP-binding cassette (ABC) transporters, implicated in cholesterol efflux. Recent data showed that LXR agonists inhibit the proliferation of multiple types of human cancer cells. However, whether these effects are related to cholesterol efflux has not yet been elucidated.
Effects of two LXR agonists (TO901317 and 22(R)-hydroxycholesterol [22(R)-HC]) on proliferation, apoptosis and cholesterol efflux were examined in MCF-7 breast cancer cells.
Treatment with LXR agonists (TO901317 at 20 μM and 22(R)-HC at 2 μg/ml) inhibited proliferation and induced apoptosis of MCF-7 cells. Furthermore, LXR activation resulted in an increase in gene and protein levels of ABCG1 transporters and in cholesterol efflux to isolated high-density lipoprotein (HDL), without affecting the ABCA1/APOA-I mediated efflux. Under these conditions, a remarkable reduction of intracellular and membrane-associated cholesterol levels was observed.
LXR activation in MCF-7 cells could deprive cells of cholesterol, required for their growth, by stimulating its efflux, resulting in the inhibition of cell proliferation and in stimulation of apoptosis.
肝 X 受体 (LXR) 通过诱导 ATP 结合盒 (ABC) 转运蛋白的表达，在胆固醇逆转运中发挥关键作用，这些转运蛋白与胆固醇外排有关。最近的数据表明，LXR 激动剂抑制多种类型的人类癌细胞的增殖。然而，这些作用是否与胆固醇外排有关尚未阐明。
在 MCF-7 乳腺癌细胞中，研究了两种 LXR 激动剂 (TO901317 和 22(R)-羟基胆固醇 [22(R)-HC]) 对增殖、凋亡和胆固醇外排的影响。
LXR 激动剂（TO901317 为 20 μM，22(R)-HC 为 2 μg/ml）处理抑制 MCF-7 细胞的增殖并诱导其凋亡。此外，LXR 激活导致 ABCG1 转运蛋白的基因和蛋白水平增加，胆固醇向分离的高密度脂蛋白 (HDL) 外排增加，而不影响 ABCA1/APOA-I 介导的外排。在这些条件下，观察到细胞内和膜相关胆固醇水平的显著降低。
在 MCF-7 细胞中激活 LXR 可以通过刺激胆固醇外排来剥夺细胞生长所需的胆固醇，从而抑制细胞增殖并刺激细胞凋亡。
