Stewart LaMonica V, Weigel Nancy L
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Exp Biol Med (Maywood). 2004 Apr;229(4):277-84. doi: 10.1177/153537020422900401.
Vitamin D and its metabolites are best known for their actions in calcium and bone metabolism. However, epidemiological studies have suggested that an increased prostate cancer risk is associated with decreased production of vitamin D. In vitro and in vivo studies have shown that the biologically active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (1,25D), inhibits proliferation of cancer cells derived from multiple tissues, including the prostate. Although the mechanisms underlying the growth inhibitory effects of 1,25D have not been fully elucidated, in prostate cancer cells 1,25D reduces cell growth via a number of cellular pathways, including cell cycle arrest, induction of apoptosis, and altered activation of growth factor signaling. The hypercalcemia induced by 1,25D in vivo limits its use clinically as a therapeutic agent. However, several 1,25D analogs have been developed that reduce prostate tumor growth in rodent xenograft models without causing hypercalcemia. Additional studies are required in order to determine whether these 1,25D analogs will be useful therapeutic agents for the treatment of prostate cancer.
维生素D及其代谢产物因其在钙和骨代谢中的作用而最为人所知。然而，流行病学研究表明，前列腺癌风险增加与维生素D生成减少有关。体外和体内研究表明，维生素D的生物活性形式1α,25-二羟基维生素D3（1,25D）可抑制包括前列腺在内的多种组织来源的癌细胞增殖。尽管1,25D生长抑制作用的潜在机制尚未完全阐明，但在前列腺癌细胞中，1,25D通过多种细胞途径减少细胞生长，包括细胞周期停滞、诱导凋亡以及改变生长因子信号的激活。1,25D在体内诱导的高钙血症限制了其在临床上作为治疗剂的应用。然而，已经开发出几种1,25D类似物，它们在啮齿动物异种移植模型中可减少前列腺肿瘤生长而不引起高钙血症。为了确定这些1,25D类似物是否将成为治疗前列腺癌的有用治疗剂，还需要进行更多研究。
