Yu D M, Tokuda N, Naito S, Yoshikawa M, Takahashi K, Uozumi J, Kumazawa J
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Int J Urol. 1998 Nov;5(6):595-600. doi: 10.1111/j.1442-2042.1998.tb00418.x.
In addition to its role in calcium and phosphorus metabolism, calcitriol (1,25-dihydroxyvitamin D3; 1,25-D3) demonstrates multiple effects on cell proliferation/differentiation by expressing major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1). It has recently been reported that 1,25-D3 inhibits the growth of prostatic cancer (PCa) cells. In this study we examined the effect of 1,25-D3 on both the growth and expression of HLA-ABC, HLA-DR and ICAM-1 antigens in PCa cells.
Four human PCa cell lines (PC-3, PPC-1, ALVA-41 and ALVA-101) were examined. The cell numbers were enumerated, and the effects of interferon-y (IFN-gamma) and 1,25-D3 on the expression of HLA-ABC, HLA-DR and ICAM-1 were quantitated by flow cytometry.
A dose-dependent antiproliferative effect of 1,25-D3 was found in all PCa cells lines except ALVA-41.1,25-D3 was approximately 10 times as potent as its analogue 24,25-dihydroxyvitamin D3 in inhibiting the growth of PC-3 cells. Also, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-D3 receptor, indicating that the antiproliferative effect may require a receptor-ligand interaction. HLA-ABC was expressed in PC-3, ALVA-41 and ALVA-101, but not in PPC-1 cells, while HLA-DR was not expressed on any of the tested cells. IFN-gammacould enhance or induce HLA-ABC but not HLA-DR expression in the tested cells. ICAM-1 was expressed in all cells and slightly upregulated by IFN-gamma.
In this study 1,25-D3 had an antiproliferative effect on 3 of the 4 examined PCa cell lines.
除了在钙和磷代谢中发挥作用外，骨化三醇（1,25 - 二羟基维生素D3；1,25 - D3）通过表达主要组织相容性复合体（MHC）抗原和细胞间黏附分子 - 1（ICAM - 1），对细胞增殖/分化具有多种影响。最近有报道称，1,25 - D3可抑制前列腺癌细胞（PCa）的生长。在本研究中，我们检测了1,25 - D3对PCa细胞生长以及HLA - ABC、HLA - DR和ICAM - 1抗原表达的影响。
检测了四种人PCa细胞系（PC - 3、PPC - 1、ALVA - 41和ALVA - 101）。对细胞数量进行计数，并通过流式细胞术定量干扰素 - γ（IFN - γ）和1,25 - D3对HLA - ABC、HLA - DR和ICAM - 1表达的影响。
在除ALVA - 41之外的所有PCa细胞系中均发现1,25 - D3具有剂量依赖性的抗增殖作用。在抑制PC - 3细胞生长方面，1,25 - D3的效力约为其类似物24,25 - 二羟基维生素D3的10倍。此外，这些化合物的相对抑制能力与其对1,25 - D3受体的结合亲和力强度平行，表明抗增殖作用可能需要受体 - 配体相互作用。HLA - ABC在PC - 3、ALVA - 41和ALVA - 101中表达，但在PPC - 1细胞中不表达，而HLA - DR在任何测试细胞中均未表达。IFN - γ可增强或诱导测试细胞中HLA - ABC的表达，但不能诱导HLA - DR的表达。ICAM - 1在所有细胞中均有表达，并被IFN - γ轻微上调。
在本研究中，1,25 - D3对所检测的4种PCa细胞系中的3种具有抗增殖作用。
