Melanoma cell growth inhibition and melanocortin receptor downregulation induced by selective and non-selective retinoids
Melanoma cell growth inhibition and melanocortin receptor downregulation induced by selective and non-selective retinoids
复制标题
DOI：
10.1097/00008390-199804000-00003
复制
发表时间：
1998-04-01
影响因子：
2.2
通讯作者：
Eberle, AN
中科院分区：
文献类型：
--
作者：
Siegrist, W;Hintermann, E;Eberle, AN
本研究的目的是研究不同维甲酸受体特异性的维甲酸类似物对人D10和Cloudman S91小鼠黑色素瘤细胞生长的影响。我们比较了生长抑制作用与类维生素A下调黑皮质素受体（MC 1-R）细胞表面表达的能力。视黄酸受体（RAR）-γ-选择性类维生素A发挥最突出的生长作用，与高达68%和69%的抑制，在D10和S91细胞，分别。类维生素A X受体（RXR）的选择性化合物抑制细胞生长只有14%和23%，分别在D10和S91细胞。RAR α和RAR β选择性化合物的生长抑制在两种细胞中均低于10%。在D10细胞中，RAR γ选择性类维生素A也能最有效地诱导MC 1-R下调（相对于对照组为84%）。RAR α、RAR β和RXR选择性激动剂在这些细胞中仅诱导16-24%的MC 1-R下调。在S91细胞中，MC 1-R下调的模式完全不同。RXR选择性化合物的活性最高（85%），其次是RAR α选择性激动剂（58%），RAR γ选择性化合物（47%），最后是RAR β选择性激动剂（29%）。我们的结论是RAR γ-选择性类维生素A可能有潜力作为黑色素瘤的治疗药物。S91细胞生长抑制和MC 1-R下调的不同选择性曲线表明，这两种维甲酸的作用并不直接依赖于彼此。(C)1998 Lippincott-Raven出版社。
The purpose of this study was to investigate the effects of retinoid analogues with different retinoid receptor specifity on the growth of human D10 and Cloudman S91 mouse melanoma cells. We compared the growth inhibitory effects with the ability of retinoids to downregulate cell surface expression of the melanocortin receptor (MC1-R). Retinoic acid receptor (RAR)-gamma-selective retinoids exerted the most prominent growth effects, with up to 68% and 69% inhibition in D10 and S91 cells, respectively. A retinoid X receptor (RXR)-selective compound inhibited cell growth by only 14% and 23% in D10 and S91 cells, respectively. Growth inhibition by RAR alpha- and RAR beta-selective compounds was below 10% in both cells. In D10 cells, MC1-R downregulation was also induced most effectively by an RAR gamma-selective retinoid (84% relative to controls). RAR alpha-, RAR beta- and RXR-selective agonists induced only 16-24% MC1-R downregulation in these cells. The pattern for MC1-R downregulation was completely different in S91 cells. The RXR-selective compound was the most active (85%), followed by the RAR alpha-selective agonist (58%), the RAR gamma-selective compound (47%), and finally by the RAR beta-selective agonist (29%). We conclude that RAR gamma-selective retinoids may have potential as therapeutic agents in melanoma. Different selectivity profiles for growth inhibition and MC1-R downregulation in S91 cells suggest that these two retinoid effects are not directly dependent on each other. (C) 1998 Lippincott-Raven Publishers.