Blutt S E, Allegretto E A, Pike J W, Weigel N L
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Endocrinology. 1997 Apr;138(4):1491-7. doi: 10.1210/endo.138.4.5063.
Recent studies have suggested that the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, can inhibit the growth and/or induce the differentiation of a variety of cell types and that these characteristics might be useful in the treatment of some cancers. Retinoids also promote the differentiation and inhibit the growth of some cells. That the vitamin D receptor acts as a heterodimer with the retinoid X receptor (RXR) suggests that there may be functional interactions between 1,25-dihydroxyvitamin D3 and retinoids. In this study, we show that the combination of 1,25-dihydroxyvitamin D3 and 9-cis retinoic acid synergistically inhibits the growth of LNCaP prostate cancer cells. That this effect is mediated by RXR rather than retinoic acid receptors was shown using RXR- and retinoic acid receptor-specific ligands. The vitamin D3 analog, EB1089, inhibited growth more effectively than 1,25-dihydroxyvitamin D3 and also acted synergistically with 9-cis-retinoic acid. These treatments caused cells to accumulate in the G1 phase of the cell cycle, suggesting that 1,25-dihydroxyvitamin D3 can regulate one or more factors critical for the G1/S transition.
近期研究表明，维生素D3的活性代谢产物1,25 - 二羟基维生素D3能够抑制多种细胞类型的生长和/或诱导其分化，并且这些特性可能在某些癌症的治疗中发挥作用。维甲酸也能促进某些细胞的分化并抑制其生长。维生素D受体与维甲酸X受体（RXR）形成异源二聚体，这表明1,25 - 二羟基维生素D3与维甲酸之间可能存在功能相互作用。在本研究中，我们发现1,25 - 二羟基维生素D3与9 - 顺式维甲酸联合使用可协同抑制LNCaP前列腺癌细胞的生长。使用RXR和维甲酸受体特异性配体表明，这种效应是由RXR而非维甲酸受体介导的。维生素D3类似物EB1089比1,25 - 二羟基维生素D3更有效地抑制细胞生长，并且也与9 - 顺式维甲酸协同发挥作用。这些处理导致细胞在细胞周期的G1期积累，这表明1,25 - 二羟基维生素D3可以调节一个或多个对G1/S转换至关重要的因子。
