Lundqvist Johan, Norlin Maria, Wikvall Kjell
Department of Pharmaceutical Biosciences, Division of Biochemistry, Box 578, University of Uppsala, SE-751 23 Uppsala, Sweden.
Biochim Biophys Acta. 2011 Apr;1811(4):263-70. doi: 10.1016/j.bbalip.2011.01.004. Epub 2011 Jan 22.
It is well-known that 1α,25-dihydroxyvitamin D(3) and analogs exert anti-proliferative and pro-differentiating effects and these compounds have therefore been proposed to be of potential use as anti-cancer agents. Due to its effects on aromatase gene expression and enzyme activity, 1α,25-dihydroxyvitamin D(3) has been proposed as an interesting substance in breast cancer treatment and prevention. In the present study, we have examined the effects of 1α,25-dihydroxyvitamin D(3) on estrogen and androgen metabolism in adrenocortical NCI-H295R cells, breast cancer MCF-7 cells and prostate cancer LNCaP cells. The NCI-H295R cell line has been proposed as a screening tool to study endocrine disruptors. We therefore studied whether this cell line reacted to 1α,25-dihydroxyvitamin D(3) treatment in the same way as cells from important endocrine target tissues. 1α,25-Dihydroxyvitamin D(3) exerted cell line-specific effects on estrogen and androgen metabolism. In breast cancer MCF-7 cells, aromatase gene expression and estradiol production were decreased, while production of androgens was markedly increased. In NCI-H295R cells, 1α,25-dihydroxyvitamin D(3) stimulated aromatase expression and decreased dihydrotestosterone production. In prostate cancer LNCaP cells, aromatase expression increased after the same treatment, as did production of testosterone and dihydrotestosterone. In summary, our data show that 1α,25-dihydroxyvitamin D(3) exerts tissue-specific effects on estrogen and androgen production and metabolism. This is important knowledge about 1α,25-dihydroxyvitamin D(3) as an interesting substance for further research in the field of breast cancer prevention and treatment. Furthermore, the observed cell line-specific effects are of importance in the discussion about NCI-H295R cells as a model for effects on estrogen and androgen metabolism.
众所周知，1α,25 - 二羟基维生素D(3)及其类似物具有抗增殖和促分化作用，因此这些化合物被认为有可能用作抗癌药物。由于其对芳香化酶基因表达和酶活性的影响，1α,25 - 二羟基维生素D(3)被认为是乳腺癌治疗和预防中一种有意义的物质。在本研究中，我们检测了1α,25 - 二羟基维生素D(3)对肾上腺皮质NCI - H295R细胞、乳腺癌MCF - 7细胞和前列腺癌LNCaP细胞中雌激素和雄激素代谢的影响。NCI - H295R细胞系已被提议作为研究内分泌干扰物的筛选工具。因此，我们研究了该细胞系对1α,25 - 二羟基维生素D(3)处理的反应是否与重要内分泌靶组织的细胞相同。1α,25 - 二羟基维生素D(3)对雌激素和雄激素代谢具有细胞系特异性作用。在乳腺癌MCF - 7细胞中，芳香化酶基因表达和雌二醇生成减少，而雄激素生成显著增加。在NCI - H295R细胞中，1α,25 - 二羟基维生素D(3)刺激芳香化酶表达并减少二氢睾酮生成。在前列腺癌LNCaP细胞中，相同处理后芳香化酶表达增加，睾酮和二氢睾酮生成也增加。总之，我们的数据表明1α,25 - 二羟基维生素D(3)对雌激素和雄激素的生成及代谢具有组织特异性作用。这是关于1α,25 - 二羟基维生素D(3)作为乳腺癌预防和治疗领域进一步研究的有意义物质的重要知识。此外，观察到的细胞系特异性作用在关于NCI - H295R细胞作为雌激素和雄激素代谢影响模型的讨论中具有重要意义。
