Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT, 06269-3092, USA.
Mol Cell Biochem. 2019 Jan;450(1-2):75-85. doi: 10.1007/s11010-018-3374-0. Epub 2018 Jun 6.
Calcitriol, vitamin D3 (VD3), and structurally related VD3 analogues are inhibitors of Hh signaling in multiple contexts and are promising anti-cancer agents in Hh-dependent forms of cancer; however, the cellular mechanisms through which these compounds regulate Hh signal transmission are not clearly defined. Previous studies in this area have implicated both Smoothened, a key mediator of Hh signaling, and the vitamin D receptor (VDR) as potential mediators of Hh inhibition for this class of seco-steroids. We have performed a series of in vitro studies to more fully probe the cellular mechanisms that govern seco-steroid-mediated inhibition of Hh signaling. Our results support a role for both the Hh and VDR pathways in this process, as well as the possibility that other, as yet unidentified proteins, are also central to seco-steroid-mediated inhibition of Hh signaling.
骨化三醇、维生素 D3（VD3）和结构相关的 VD3 类似物是多种情况下 Hh 信号的抑制剂，并且是 Hh 依赖性癌症的有前途的抗癌药物；然而，这些化合物调节 Hh 信号转导的细胞机制尚不清楚。该领域的先前研究表明，Hh 信号的关键介质 Smoothened 和维生素 D 受体（VDR）都是此类甾体的 Hh 抑制的潜在介质。我们进行了一系列体外研究，以更充分地探究控制甾体介导的 Hh 信号抑制的细胞机制。我们的结果支持 Hh 和 VDR 途径在该过程中的作用，以及其他尚未鉴定的蛋白质也可能是甾体介导的 Hh 信号抑制的核心。
