文章：

喉癌细胞代谢25-羟基维生素D3并通过依赖雌激素受体水平的机制对24R,25-二羟基维生素D3产生应答

Laryngeal Cancer Cells Metabolize 25-Hydroxyvitamin D3and Respond to 24R,25-dihydroxyvitamin D3via a Mechanism Dependent on Estrogen Receptor Levels

原文发布日期：24 April 2024

DOI: 10.3390/cancers16091635

类型: Article

开放获取: 是

英文摘要：

Studies have evaluated vitamin D3’s therapeutic potential in estrogen-responsive cancers, with conflicting findings. We have shown that the proliferation of breast cancer cells is regulated by 24R,25-dihydroxyvitamin D3(24R,25(OH)2D3) depending on estrogen receptor alpha 66 (ERα66) expression, suggesting that this could also be the case for estrogen-sensitive laryngeal cancer cells. Accordingly, we examined levels of ERα isoforms in ERα66-positive UM-SCC-12 and ERα66-negative UM-SCC-11A cells and their response to 24R,25(OH)2D3. 24R,25(OH)2D3stimulated proliferation, increased the expression of metastatic markers, and inhibited apoptosis in UM-SCC-12 cells while having the opposite effect in UM-SCC-11A cells. To evaluate if vitamin metabolites could act via autocrine/paracrine mechanisms, we assessed the expression, protein levels, and activity of vitamin D3hydroxylases CYP24A1 and CYP27B1. Both cell types expressed both mRNAs; but the levels of the enzymes and their activities were differentially regulated by estrogen. ERα66-negative UM-SCC-11A cells produced more 24,25(OH)2D3than UM-SCC-12 cells, but comparable levels of 1,25(OH)2D3when treated with 25(OH)D3These results suggest that the regulation of vitamin D3metabolism in laryngeal cancer cells is modulated by ERα66 expression, and support a role for 24R,25(OH)2D3as an autocrine/paracrine regulator of laryngeal cancer. The local metabolism of 25(OH)D3should be considered when determining the potential of vitamin D3in laryngeal cancer.

摘要翻译： 

已有研究评估了维生素D3在雌激素反应性癌症中的治疗潜力，但结果存在矛盾。我们发现乳腺癌细胞的增殖受24R,25-二羟基维生素D3（24R,25(OH)2D3）调控，且该调控作用依赖于雌激素受体α66（ERα66）的表达，提示这一机制可能同样存在于雌激素敏感的喉癌细胞中。为此，我们检测了ERα66阳性细胞UM-SCC-12与ERα66阴性细胞UM-SCC-11A中ERα亚型的表达水平及其对24R,25(OH)2D3的反应。结果显示，24R,25(OH)2D3能促进UM-SCC-12细胞增殖、增加转移标志物表达并抑制细胞凋亡，而在UM-SCC-11A细胞中则产生相反效应。为探究维生素代谢物是否通过自分泌/旁分泌机制发挥作用，我们评估了维生素D3羟化酶CYP24A1和CYP27B1的表达水平、蛋白含量及活性。两种细胞均表达这两种酶的mRNA，但酶水平及其活性受雌激素的差异性调控。当使用25(OH)D3处理时，ERα66阴性的UM-SCC-11A细胞比UM-SCC-12细胞产生更多24,25(OH)2D3，但两者生成的1,25(OH)2D3水平相当。这些结果表明，喉癌细胞中维生素D3代谢的调控受ERα66表达的影响，并支持24R,25(OH)2D3作为喉癌自分泌/旁分泌调节因子的作用。在评估维生素D3对喉癌的潜在作用时，应考虑25(OH)D3的局部代谢过程。

原文链接：

Laryngeal Cancer Cells Metabolize 25-Hydroxyvitamin D3and Respond to 24R,25-dihydroxyvitamin D3via a Mechanism Dependent on Estrogen Receptor Levels