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The coupling of epidermal growth factor receptor down regulation by 1alpha,25-dihydroxyvitamin D3 to the hormone-induced cell cycle arrest at the G1-S checkpoint in ovarian cancer cells.1α,25-二羟维生素 D3 下调表皮生长因子受体与激素诱导的卵巢癌细胞 G1-S 检查点细胞周期阻滞的偶联作用。
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CYP24A1 is an independent prognostic marker of survival in patients with lung adenocarcinoma.CYP24A1 是肺腺癌患者生存的独立预后标志物。
Clin Cancer Res. 2011 Feb 15;17(4):817-26. doi: 10.1158/1078-0432.CCR-10-1789. Epub 2010 Dec 17.
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Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer.核维生素 D 受体表达与非小细胞肺癌患者的生存改善相关。
J Steroid Biochem Mol Biol. 2011 Jan;123(1-2):30-6. doi: 10.1016/j.jsbmb.2010.10.002. Epub 2010 Oct 16.
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Vitamin D analogues targeting CYP24 in chronic kidney disease.针对慢性肾脏病中 CYP24 的维生素 D 类似物。
J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):13-9. doi: 10.1016/j.jsbmb.2010.03.065. Epub 2010 Mar 27.
5
A downstream intergenic cluster of regulatory enhancers contributes to the induction of CYP24A1 expression by 1alpha,25-dihydroxyvitamin D3.下游基因间调控增强子簇有助于 1α,25-二羟维生素 D3 诱导 CYP24A1 表达。
J Biol Chem. 2010 May 14;285(20):15599-15610. doi: 10.1074/jbc.M110.119958. Epub 2010 Mar 17.
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Vorinostat increases carboplatin and paclitaxel activity in non-small-cell lung cancer cells.伏立诺他增加非小细胞肺癌细胞中卡铂和紫杉醇的活性。
Int J Cancer. 2010 Feb 1;126(3):743-55. doi: 10.1002/ijc.24759.
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Vitamin D's role in cell proliferation and differentiation.维生素D在细胞增殖和分化中的作用。
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Vitamin D and prevention of breast cancer.维生素D与乳腺癌的预防
Acta Pharmacol Sin. 2007 Sep;28(9):1373-82. doi: 10.1111/j.1745-7254.2007.00700.x.
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Inhibition of lung carcinogenesis by 1alpha,25-dihydroxyvitamin D3 and 9-cis retinoic acid in the A/J mouse model: evidence of retinoid mitigation of vitamin D toxicity.1α,25 - 二羟基维生素D3和9 - 顺式视黄酸在A/J小鼠模型中对肺癌发生的抑制作用：视黄酸减轻维生素D毒性的证据
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Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1;Pten mutant mice.维生素D可抑制Nkx3.1；Pten基因双突变小鼠前列腺上皮内瘤变的形成。
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CYP24 抑制可保留肺癌细胞中 1α,25-二羟维生素 D(3) 的抗增殖信号。

CYP24 inhibition preserves 1α,25-dihydroxyvitamin D(3) anti-proliferative signaling in lung cancer cells.

机构信息

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Mol Cell Endocrinol. 2012 May 15;355(1):153-61. doi: 10.1016/j.mce.2012.02.006. Epub 2012 Feb 22.

DOI:10.1016/j.mce.2012.02.006
PMID:22386975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3312998/
Abstract

Human lung tumors aberrantly express the 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-catabolizing enzyme, CYP24. We hypothesized that CYP24 reduces 1,25(OH)(2)D(3)-mediated transcription and allows lung cancer cells to escape its growth-inhibitory action. To test this, H292 lung cancer cells and the CYP24-selective inhibitor CTA091 were utilized. In H292 cells, CTA091 reduces 1,25(OH)(2)D(3) catabolism, significantly increases 1,25(OH)(2)D(3)-mediated growth inhibition, and increases 1,25(OH)(2)D(3) effects on induced and repressed genes in gene expression profiling studies. Pathway mapping of repressed genes uncovered cell cycle as a predominant 1,25(OH)(2)D(3) target. In H292 cells, 1,25(OH)(2)D(3) significantly decreases cyclin E2 levels and induces G(0)/G(1) arrest. A broader set of cyclins is down-regulated when 1,25(OH)(2)D(3) is combined with CTA091, and cell cycle arrest further increases. Effects of CTA091 on 1,25(OH)(2)D(3) signaling are vitamin D receptor-dependent. These data provide evidence that CYP24 limits 1,25(OH)(2)D(3) anti-proliferative signaling in cancer cells, and suggest that CTA091 may be beneficial in preserving 1,25(OH)(2)D(3) action in lung cancer.

摘要

人肺肿瘤异常表达 1α,25-二羟维生素 D(3)（1,25(OH)(2)D(3)）-代谢酶，CYP24。我们假设 CYP24 降低 1,25(OH)(2)D(3)介导的转录，使肺癌细胞逃避其生长抑制作用。为了验证这一点，使用了 H292 肺癌细胞和 CYP24 选择性抑制剂 CTA091。在 H292 细胞中，CTA091 减少 1,25(OH)(2)D(3)代谢，显著增加 1,25(OH)(2)D(3)介导的生长抑制，并增加 1,25(OH)(2)D(3)对基因表达谱研究中诱导和抑制基因的作用。受抑制基因的通路映射揭示细胞周期是 1,25(OH)(2)D(3)的主要靶标。在 H292 细胞中，1,25(OH)(2)D(3)显著降低细胞周期蛋白 E2 水平并诱导 G(0)/G(1)停滞。当 1,25(OH)(2)D(3)与 CTA091 联合使用时，更广泛的细胞周期蛋白下调，细胞周期停滞进一步增加。CTA091 对 1,25(OH)(2)D(3)信号的影响依赖于维生素 D 受体。这些数据提供了证据表明 CYP24 限制了癌症细胞中 1,25(OH)(2)D(3)的抗增殖信号，并且表明 CTA091 可能有益于维持肺癌中 1,25(OH)(2)D(3)的作用。