Vitamin D metabolism and action in the prostate: implications for health and disease.
Vitamin D metabolism and action in the prostate: implications for health and disease.
复制标题
维生素D代谢和前列腺作用：对健康和疾病的影响。
DOI：
10.1016/j.mce.2011.05.010
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发表时间：
2011-12-05
影响因子：
4.1
通讯作者：
Feldman, David
中科院分区：
文献类型：
--
作者：
Swami, Srilatha;Krishnan, Aruna V.;Feldman, David
前列腺癌（PCa）是世界范围内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缺乏是前列腺癌发生和/或进展的危险因素。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，尽管临床前研究提供了抗癌活性的有力指示，但在男性中治疗益处的证据仍然缺乏。维生素D的抗增殖和促分化特性归因于骨化三醇[1,25(OH)2D3]，这是维生素D的激素活性形式，通过维生素D受体（VDR）起作用。维生素D在靶组织中的代谢由两个关键酶介导：1α-羟化酶（CYP27B1）和24-羟化酶（CYP24），前者催化25(OH)D合成骨化三醇，后者催化骨化三醇转化为活性较低的代谢物的第一步。许多因素影响骨化三醇合成和分解代谢的平衡，一些策略，如骨化三醇与其他药物联合治疗，已被探索用于治疗PCa并降低其风险。本文概述了影响维生素D及其代谢物在治疗和/或预防前列腺癌中的生物作用的一些关键因素。
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 pre-clinical 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)2D3], 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.
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