Rocker D, Ravid A, Liberman U A, Garach-Jehoshua O, Koren R
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Mol Cell Endocrinol. 1994 Dec;106(1-2):157-62. doi: 10.1016/0303-7207(94)90198-8.
We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the cytotoxic action of TNF on MCF-7 human breast cancer cells and on adult bovine aortic endothelial cells. 1,25(OH)2D3 increased the effect of TNF on MCF-7 cells but not on endothelial cells over a wide TNF concentration range. At a suboptimal concentration (1 ng/ml) the potentiation was twofold. The effect of 1,25(OH)2D3 was specific, dose-dependent and apparent at a physiological concentration (0.1 nM) of the hormone. The potentiating effect of 1,25(OH)2D3 on TNF action was abolished by cycloheximide indicating that their interaction requires protein synthesis. Addition of 1,25(OH)2D3 13 h after TNF in a 28-h assay was sufficient to induce its full potentiating effect indicating that the hormone modulates a late event in the cytokine's action. These data suggest that some of the in vivo antitumor effects of 1,25(OH)2D3 may be due to an increase in the anticancer activity of the immune system.
我们研究了1,25 - 二羟基维生素D3（1,25(OH)2D3）对肿瘤坏死因子（TNF）作用于MCF - 7人乳腺癌细胞及成年牛主动脉内皮细胞的细胞毒性作用的影响。在较宽的TNF浓度范围内，1,25(OH)2D3增强了TNF对MCF - 7细胞的作用，但对内皮细胞没有这种作用。在亚最佳浓度（1纳克/毫升）时，增强作用为两倍。1,25(OH)2D3的作用具有特异性、剂量依赖性，且在该激素的生理浓度（0.1纳摩尔）时明显。放线菌酮可消除1,25(OH)2D3对TNF作用的增强效应，这表明它们的相互作用需要蛋白质合成。在28小时的实验中，在TNF作用13小时后添加1,25(OH)2D3足以诱导其充分的增强效应，这表明该激素调节细胞因子作用的一个晚期事件。这些数据表明，1,25(OH)2D3在体内的一些抗肿瘤作用可能是由于免疫系统抗癌活性的增强。
