Goldman R
Cancer Res. 1985 Jul;45(7):3118-24.
1 alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and retinoic acid (RA) induce a high-phagocytic phenotype in the macrophage-like tumor cell line P388D1. A concurrent cultivation of P388D1 cells in the presence of suboptimal concentrations of both agents led to an extent of induction of phagocytic activity that surpassed the additive effect of either of the agents alone; i.e., 1,25(OH)2D3 and RA synergistically induce the phagocytic capability of P388D1 cells. Dexamethasone and 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (TPA) did not induce a high-phagocytic phenotype in P388D1 cells and affected differentially the high-phagocytic phenotype induced by RA and 1,25(OH)2D3. Dexamethasone inhibited the phagocytic activity induced by RA (80% at 24 h), while it had small suppressive effects on that induced by 1,25(OH)2D3. TPA suppressed the phagocytic activity induced by RA (60% within 96 h) while potentiating the expression of the high-phagocytic phenotype induced by 1,25(OH)2D3 (50% increase with 96 h). The observed effects did not involve modulation of prostaglandin synthesis or intracellular cyclic adenosine 3':5'-monophosphate. Expression of transglutaminase activity in P388D1 cells was also modulated differentially by the four agents; 1,25(OH)2D3 treatment had no effect on enzyme level, RA and TPA suppressed it, and dexamethasone increased it. The data suggest that: 1,25(OH)2D3 and RA act via disparate mechanisms that can operate simultaneously; the elements induced in P388D1 cells by 1,25(OH)2D3 and RA, and which are responsible for the phagocytic activity, differ in their sensitivity to dexamethasone and TPA; and transglutaminase activity in P388D1 cells is readily manipulable, but there seems to be no straightforward correlation between the level of its activity and the phagocytic capability of the cells or their rate of proliferation.
1α,25 - 二羟基维生素D3 [1,25(OH)2D3] 和视黄酸 (RA) 可诱导巨噬细胞样肿瘤细胞系P388D1呈现高吞噬表型。在两种药物亚最佳浓度存在的情况下同时培养P388D1细胞，所诱导的吞噬活性程度超过了单独使用任何一种药物的累加效应；即，1,25(OH)2D3和RA协同诱导P388D1细胞的吞噬能力。地塞米松和4β - 佛波醇 - 12β - 肉豆蔻酸 - 13α - 乙酸酯 (TPA) 不会在P388D1细胞中诱导高吞噬表型，并且对RA和1,25(OH)2D3诱导的高吞噬表型有不同影响。地塞米松抑制RA诱导的吞噬活性（24小时时抑制80%），而对1,25(OH)2D3诱导的吞噬活性只有较小的抑制作用。TPA抑制RA诱导的吞噬活性（96小时内抑制60%），同时增强1,25(OH)2D3诱导的高吞噬表型的表达（96小时时增加50%）。观察到的这些效应不涉及前列腺素合成或细胞内环状腺苷3':5'-单磷酸的调节。四种药物对P388D1细胞中转谷氨酰胺酶活性的表达也有不同调节作用；1,25(OH)2D3处理对酶水平无影响，RA和TPA抑制该酶活性，地塞米松则增加其活性。数据表明：1,25(OH)2D3和RA通过不同机制起作用，这些机制可同时发挥作用；1,25(OH)2D3和RA在P388D1细胞中诱导产生的、负责吞噬活性的成分，对地塞米松和TPA的敏感性不同；P388D1细胞中的转谷氨酰胺酶活性易于调控，但该酶活性水平与细胞的吞噬能力或增殖速率之间似乎没有直接关联。
