Vitamin D receptor and p21/WAF1 are targets of genistein and 1,25-dihydroxyvitamin D3 in human prostate cancer cells
Vitamin D receptor and p21/WAF1 are targets of genistein and 1,25-dihydroxyvitamin D3 in human prostate cancer cells
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DOI：
10.1158/0008-5472.can-03-3480
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发表时间：
2004-03-15
期刊：
影响因子：
11.2
通讯作者：
Cramer, SD
中科院分区：
文献类型：
--
作者：
Rao, A;Coan, A;Cramer, SD
本研究探讨了染料木素与1,25-二羟基维生素D-3 [1,25(OH)(2)D-3]协同抑制人前列腺癌细胞LNCaP生长的机制。我们证明1,25(OH)(2)D-3和染料木素通过增加维生素D受体的稳定性来协同上调维生素D受体蛋白。染料木黄酮和1,25(OH)(2)D-3也协同上调p21/WAF1 （p21）的水平。小干扰rna介导的p21表达下调表明，p21对于LNCaP细胞对化合物或它们的联合反应的显著生长抑制至关重要。我们得出结论，染料木素与1,25(OH)(2)D-3之间协同作用的一个机制是通过染料木素调节维生素D信号传导。
We investigated mechanisms by which genistein and 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] act synergistically to inhibit the growth of the human prostate cancer cell line LNCaP. We demonstrate that 1,25(OH)(2)D-3 and genistein cooperate to up-regulate the vitamin D receptor protein by increasing the stability of the vitamin D receptor. Genistein and 1,25(OH)(2)D-3 also cooperate to up-regulate the levels of p21/WAF1 (p21). Small interfering RNA-mediated knockdown of p21 expression showed that p21 is essential for significant growth inhibition of LNCaP cells in response to either compound or their combination. We conclude that one mechanism of synergism between genistein and 1,25(OH)(2)D-3 is through genistein modulation of vitamin D signaling.