Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mol Cell Endocrinol. 2011 Dec 5;347(1-2):61-9. doi: 10.1016/j.mce.2011.05.010. Epub 2011 Jun 1.
Prostate cancer (PCa) is the second most common cancer in men worldwide. Epidemiological, molecular, and cellular studies have implicated vitamin D deficiency as a risk factor for the development and/or progression of PCa. Studies using cell culture systems and animal models suggest that vitamin D acts to reduce the growth of PCa through regulation of cellular proliferation and differentiation. However, although preclinical studies provide a strong indication for anti-cancer activity, proof of therapeutic benefits in men is still lacking. The anti-proliferative and pro-differentiating properties of vitamin D have been attributed to calcitriol [1,25(OH)(2)D(3)], the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR). Metabolism of vitamin D in target tissues is mediated by two key enzymes: 1α-hydroxylase (CYP27B1), which catalyzes the synthesis of calcitriol from 25(OH)D and 24-hydroxylase (CYP24), which catalyzes the initial step in the conversion of calcitriol to less active metabolites. Many factors affect the balance of calcitriol synthesis and catabolism and several maneuvers, like combination therapy of calcitriol with other drugs, have been explored to treat PCa and reduce its risk. The current paper is an overview addressing some of the key factors that influence the biological actions of vitamin D and its metabolites in the treatment and/or prevention of PCa.
前列腺癌（PCa）是全球男性第二大常见癌症。流行病学、分子和细胞研究表明，维生素 D 缺乏是 PCa 发生和/或进展的一个危险因素。使用细胞培养系统和动物模型的研究表明，维生素 D 通过调节细胞增殖和分化来减少 PCa 的生长。然而，尽管临床前研究强烈表明维生素 D 具有抗癌活性，但男性的治疗益处仍缺乏证据。维生素 D 的抗增殖和促分化特性归因于 1,25-二羟维生素 D [1,25(OH)(2)D(3)]，这是维生素 D 的激素活性形式，通过维生素 D 受体（VDR）发挥作用。维生素 D 在靶组织中的代谢由两种关键酶介导：1α-羟化酶（CYP27B1），它催化 25(OH)D 合成 1,25-二羟维生素 D；24-羟化酶（CYP24），它催化 1,25-二羟维生素 D 向无活性代谢物转化的初始步骤。许多因素影响 1,25-二羟维生素 D 合成和分解代谢的平衡，已经探索了几种策略，如 1,25-二羟维生素 D 与其他药物的联合治疗，以治疗 PCa 并降低其风险。本文概述了一些关键因素，这些因素影响了维生素 D 及其代谢物在治疗和/或预防 PCa 中的生物学作用。
