Greater synergism of retinoic acid receptor (RAR) agonists with vitamin D3 than that of retinoid X receptor (RXR) agonists with regard to growth inhibition and differentiation induction in monoblastic leukemia cells.
Greater synergism of retinoic acid receptor (RAR) agonists with vitamin D3 than that of retinoid X receptor (RXR) agonists with regard to growth inhibition and differentiation induction in monoblastic leukemia cells.
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在单核细胞白血病细胞的生长抑制和分化诱导方面，视黄酸受体 (RAR) 激动剂与维生素 D3 的协同作用比类视黄酸 X 受体 (RXR) 激动剂更强。
DOI：
10.1016/s0006-2952(98)00329-3
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发表时间：
1999
影响因子：
5.8
通讯作者：
Y. Honma
中科院分区：
文献类型：
--
作者：
M. Makishima;K. Shudo;Y. Honma
维甲酸与1，25-二羟基维生素D3(1-α，25-dioh VitD3，VD3)协同诱导髓系白血病细胞分化。我们研究了视黄醇受体(RARs和RXRs)在维甲酸和VD3对人单核细胞白血病U937细胞的生长抑制和诱导分化中的作用。等谱图分析表明，两种药物在抑制细胞增殖方面具有协同作用，RAR激动剂与VD3的协同作用强于RXR激动剂。RXR激动剂单独诱导U937细胞中NBT的减少和CD11b的表达，而RAR激动剂不能。另一方面，RAR激动剂和RXR激动剂促进VD3诱导分化，但RXR激动剂需要更高的浓度。RAR拮抗剂抑制RAR激动剂+VD3诱导的分化，但不抑制RXR激动剂+VD3诱导的分化。因此，RARs和RXRs在与VD3的协同作用中发挥不同的作用。在与VD3的协同作用方面，RAR激动剂比RXR激动剂更有效，它们的联合应用可能有助于髓系白血病的分化治疗。
Retinoids and 1α,25-dihydroxyvitamin D3(VD3) cooperatively induce the differentiation of myeloid leukemia cells. We investigated the role of retinoid receptors (RARs and RXRs) in the combined effects of retinoids and VD3on growth inhibition and differentiation induction in human monoblastic leukemia U937 cells by using RAR- or RXR-selective retinoids. An isobologram analysis showed that both combinations were synergistic with regard to inhibiting the proliferation, and RAR agonists exhibited greater synergism with VD3than did RXR agonists. RXR agonists alone induced nitroblue tetrazolium (NBT) reduction and expression of CD11b in U937 cells, whereas RAR agonists alone did not. On the other hand, RAR agonists and RXR agonists enhanced the differentiation induced by VD3, but RXR agonists required higher concentrations. An RAR antagonist inhibited the differentiation induced by RAR agonists plus VD3, but not that induced by RXR agonists plus VD3. Thus, RARs and RXRs act differently in their synergism with VD3. RAR agonists are more potent than RXR agonists with regard to synergism with VD3, and their combination may be useful in differentiation therapy against myeloid leukemia.
类维生素A受体泛激动剂9-顺式视黄酸的初步临床试验。
DOI：
--
发表时间：
1996
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Miller,VA;Rigas,JR;Benedetti,FM;Verret,AL;Tong,WP;Kris,MG;Gill,GM;Loewen,GR;Truglia,JA;Ulm,EH;WarrellJr,RP
通讯作者：
WarrellJr,RP