Characterization of the effects of different retinoids on the growth and differentiation of a human melanoma cell line and selected subclones.
Characterization of the effects of different retinoids on the growth and differentiation of a human melanoma cell line and selected subclones.
复制标题
表征不同类视黄醇对人类黑色素瘤细胞系和选定亚克隆的生长和分化的影响。
作者：
F. Meyskens;B. Fuller
评估了四种不同的视黄酸[视黄醇、13-顺式视黄酸 (Ro4-3780)、β-全反式视黄酸和芳香族视黄酸乙酯 (Ro10-9359)] 对人黑色素瘤细胞系 (MIRW) 和三个亚克隆的细胞增殖（细胞数量）和生化分化（酪氨酸酶活性）的影响。所有四种类维生素A (10(-6) M) 均以相似的程度抑制亲本细胞系中的细胞增殖（36%至42%）并刺激酪氨酸酶活性（58%至72%）。相比之下，不同的类维生素A对三种衍生的黑色素瘤克隆的影响是不同的。例如，在克隆 A6 中，β-全反式视黄酸将酪氨酸酶活性刺激了 48%，但仅抑制了 7% 的细胞增殖。这种类视黄醇在其他两个亚克隆中产生了更明显的效果，刺激酪氨酸酶 135% 至 195%，并抑制生长 19% 至 33%。所有三个黑色素瘤克隆在接触 13-顺式视黄酸后均表现出酪氨酸酶活性增加（110% 至 225%）和增殖减少（37% 至 52%）。总体而言，这种类视黄醇是最有效的酪氨酸酶刺激剂，而视黄醇的活性最低，仅在三个克隆之一中轻微刺激酶活性（25%）。视黄醇在三个黑色素瘤亚克隆中的两个中抑制增殖 27% 至 33%。芳香族视黄酸乙酯提高了两个克隆中的酪氨酸酶水平，但抑制了一种黑色素瘤系中的酶。然而，所有三个克隆的细胞增殖均减少。这些结果表明，类维生素A诱导的人类黑色素瘤细胞生长和分化的变化反映了潜在的细胞差异和不同的生化相互作用。
The effect of four different retinoids [retinol, 13-cis-retinoic acid (Ro4-3780), beta-all-trans-retinoic acid, and aromatic retinoic acid ethyl ester (Ro10-9359)] on the cellular proliferation (cell number) and biochemical differentiation (tyrosinase activity) of a human melanoma cell line (MIRW) and three subclones was assessed. All four retinoids (10(-6) M) inhibited the cellular proliferation (36 to 42%) and stimulated tyrosinase activity (58 to 72%) in the parent cell line to a similar extent. In contrast, the effects of the different retinoids on three derived melanoma clones was dissimilar. For example, in clone A6, beta-all-transretinoic acid stimulated tyrosinase activity by 48% but caused only a 7% inhibition of cellular proliferation. This retinoid caused a more pronounced effect in the other two subclones, stimulating tyrosinase from 135 to 195% and inhibiting growth 19 to 33%. Al three melanoma clones demonstrated increased tyrosinase activity (110 to 225%) and reduced proliferation (37 to 52%) following exposure to 13-cis-retinoic acid. This retinoid was found overall to be the most effective stimulator of tyrosinase, while retinol was observed to be the least active, stimulating enzyme activity slightly (25%) in only one of three clones. Retinol inhibited proliferation 27 to 33% in two of three melanoma subclones. The aromatic retinoic acid ethyl ester elevated tyrosinase levels in two clones but inhibited the enzyme in one melanoma line. Cellular proliferation, however, was reduced in all three clones. These results suggest that retinoid-induced changes in human melanoma cell growth and differentiation reflect underlying cellular differences and diverse biochemical interactions.