Croxtall J D, Flower R J
Department of Biochemical Pharmacology, William Harvey Institute, Medical College of St Bartholomew's Hospital, London, U.K.
Biochem Pharmacol. 1994 Nov 1;48(9):1729-34. doi: 10.1016/0006-2952(94)90458-8.
Glucocorticoids actively inhibit the growth of A549 cells by suppressing the release of factors such as prostaglandin E2 (PGE2) necessary for their proliferation. This effect is largely mediated through induction of the protein lipocortin-1. We now show that transient transfection of A549 cells with an antisense DNA oligonucleotide targeted to a region coding the unique N-terminal portion of human lipocortin-1 blocks the induction of lipocortin-1 protein following glucocorticoid treatment and completely reverses glucocorticoid-induced suppression of cell proliferation and PGE2 release. A scrambled oligonucleotide was without effect. Continued culture of A549 cells in the presence of this oligonucleotide results in a sustained increase in cell proliferation and PGE2 release. This study reinforces the importance of lipocortin-1 as a negative modulator of cell growth and eicosanoid generation in this system.
糖皮质激素通过抑制诸如前列腺素E2（PGE2）等细胞增殖所需因子的释放，来积极抑制A549细胞的生长。这种效应很大程度上是通过诱导蛋白脂皮质素-1介导的。我们现在表明，用靶向编码人脂皮质素-1独特N端部分区域的反义DNA寡核苷酸瞬时转染A549细胞，可阻断糖皮质激素处理后脂皮质素-1蛋白的诱导，并完全逆转糖皮质激素诱导的细胞增殖抑制和PGE2释放。一个随机排列的寡核苷酸则没有效果。在这种寡核苷酸存在的情况下持续培养A549细胞，会导致细胞增殖和PGE2释放持续增加。这项研究强化了脂皮质素-1作为该系统中细胞生长和类花生酸生成的负调节剂的重要性。
