Antiproliferative effect of a vitamin D3 analog, EB1089, on HL-60 cells by the induction of TGF-β receptor

被引：24

作者：

Jung, CW

Kim, ES

Seol, JG

Park, WH

Lee, SJ

Kim, BK

Lee, YY ^{[1
]}

机构：

[1] Chung Ang Univ, Coll Med, Dept Internal Med, Seoul 156756, South Korea

[2] Seoul Natl Univ, Coll Med, Canc Res Ctr, Dept Internal Med, Seoul 110799, South Korea

[3] Han Yang Univ Hosp, Dept Internal Med, Div Hematol Oncol, Sung Dong Ku, Seoul 133792, South Korea

来源：

LEUKEMIA RESEARCH | 1999年 / 23卷 / 12期

关键词：

EB1089; HL-60; transforming growth factor-beta 1; transforming growth factor-beta receptor; vitamin D receptor; p27;

D O I：

10.1016/S0145-2126(99)00136-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

EB1089 is a novel 1,25(OH)(2)D-3 analog that has more potent antitumor properties with reduced hypercalcemic effects than 1,25(OH)(2)D-3. We investigated the role of transforming growth factor-beta 1 (TGF-beta 1) in the growth inhibition of human acute myeloid leukemia cell line, HL-60, by EB1089. Clonal growth of HL-60 cells was inhibited in a dose-dependent manner by EB1089. Although TGF-beta 1 alone slightly inhibited proliferation of HL-60 cells, the addition of TGF-beta 1 into culture treated with 10(-8) M of EB1089 showed a significant synergistic antiproliferative effect in a dose-dependent manner. EB1089 up-regulated the expression of TGF-beta receptor type I (TGF-beta RI), type II (TGF-beta RII) and TGF-beta 1. Antiproliferative effect of EB1089 was partially reversed by TGF-beta 1 neutralizing antibody (anti-TGF-beta 1). Vitamin D receptor (VDR) expression was increased by TGF-beta 1, suggesting synergistic action of TGF-beta 1 and EB1089. Combined treatment of EB1089 and TGF-beta 1 resulted in an increased expression of cyclin-dependent kinase inhibitor (CDKI), p27 protein, compared to either ligand alone. Up-regulation of p27 protein expression by either TGF-beta 1 or EB1089 was reduced by anti-TGF-beta 1. These findings suggest that TGF-beta 1 is involved in the antiproliferative effect of EB1089 on HL-60 cells. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：1105 / 1112

页数：8

共 50 条

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