1,25-Dihydroxyvitamin D-3 and 9-cis-retinoic acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G(1)
1,25-Dihydroxyvitamin D-3 and 9-cis-retinoic acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G(1)
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DOI：
10.1210/en.138.4.1491
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发表时间：
1997-04-01
期刊：
影响因子：
4.8
通讯作者：
Weigel, NL
中科院分区：
文献类型：
--
作者：
Blutt, SE;Allegretto, EA;Weigel, NL
最近的研究表明，维生素D-3的活性代谢产物1，25-二羟基维生素D-3可以抑制多种细胞类型的生长和/或诱导分化，并且这些特性可能在某些癌症的治疗中有用。维甲酸还促进某些细胞的分化和抑制某些细胞的生长。维生素D受体与类维生素A X受体（RXR）作为异二聚体起作用，这表明1，25-二羟基维生素D和类维生素A之间可能存在功能性相互作用。在这项研究中，我们表明，1，25-二羟维生素D和9-顺式维甲酸的组合协同抑制LNCaP前列腺癌细胞的生长。使用RXR和视黄酸受体特异性配体显示，这种作用由RXR而不是视黄酸受体介导。维生素D类似物EB 1089比1，25-二羟基维生素D更有效地抑制生长，并且还与B-顺式-视黄酸协同作用。这些处理导致细胞聚集在细胞周期的G（1）期，表明1，25-二羟维生素D可以调节一个或多个G（1）/S转换的关键因素。
Recent studies have suggested that the active metabolite of vitamin D-3, 1,25-dihydroxyvitamin D-3, 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 D, and retinoids. In this study, we show that the combination of 1,25-dihydroxyvitamin D, 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 D, analog, EB1089, inhibited growth more effectively than 1,25-dihydroxyvitamin D, and also acted synergistically with B-cis-retinoic acid. These treatments caused cells to accumulate in the G(1) phase of the cell cycle, suggesting that 1,25dihydroxyvitamin D, can regulate one or more factors critical for the G(1)/S transition.