Efficacy of Vitamin D compounds to modulate estrogen receptor negative breast cancer growth and invasion
Efficacy of Vitamin D compounds to modulate estrogen receptor negative breast cancer growth and invasion
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DOI：
10.1016/s0960-0760(03)00028-1
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发表时间：
2003-02-01
影响因子：
4.1
通讯作者：
Welsh, J
中科院分区：
文献类型：
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作者：
Flanagan, L;Packman, K;Welsh, J
在雌激素受体 (ER) 阳性乳腺癌细胞（例如 MCF-7 细胞）中，1,25(OH)(2)D-3 (1,25D(3)) 的抗肿瘤作用可能继发于雌激素介导的生存信号的破坏。如果是这样，那么雌激素非依赖性乳腺癌细胞对 1,25D(3) 介导的生长停滞的敏感性可能会降低。这些研究的目的是确定 1,25D(3) 和 EB1089 对 ER 阴性、侵袭性人乳腺癌细胞系 SUM-159PT 的影响。在 p27 和 p21 水平升高后，1,25D(3) 和 EB1089 减少了 SUM-159PT 细胞的生长。 1,25D(3) 介导的 SUM-159PT 细胞凋亡与膜结合 bax 的富集、细胞色素 c 从线粒体到细胞质的重新分布以及 PARP 裂解有关。 1,25D(3) 和EB1089 还抑制SUM-159PT 细胞通过8 muM Matrigel 膜的侵袭。在临床前研究中，EB1089 显着降低了裸鼠中 SUM-159PT 异种移植物的生长。 EB1089 治疗小鼠的肿瘤尺寸减小与增殖减少和 DNA 碎片增加有关。我们的数据支持维生素 D-3 化合物通过独立于雌激素信号传导的机制触发细胞凋亡的概念。这些研究表明，单独或与其他药物联合使用基于维生素 D-3 的疗法可能有益于治疗雌激素非依赖性乳腺癌。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
In estrogen receptor (ER) positive breast cancer cells such as MCF-7 cells, the anti-tumor effects of 1,25(OH)(2)D-3 (1,25D(3)) may be secondary to disruption of estrogen mediated survival signals. If so, then sensitivity to 1,25D(3) mediated growth arrest could be reduced in estrogen independent breast cancer cells. The aim of these studies was to determine the effects of 1,25D(3) and EB1089 on the ER negative, invasive human breast cancer cell line SUM-159PT. 1,25D(3) and EB1089 reduced SUM-159PT cell growth subsequent to elevation of p27 and p21 levels. 1,25D(3) mediated apoptosis of SUM-159PT cells was associated with an enrichment of membrane bound bax, a redistribution of cytochome c from the mitochondria to the cytosol and PARP cleavage. 1,25D(3) and EB1089 also inhibited SUM-159PT cell invasion through an 8 muM Matrigel membrane. In pre-clinical studies, EB1089 dramatically reduced the growth of SUM-159PT xenografts in nude mice. The decreased size of tumors from EB1089 treated mice was associated with decreased proliferation and increased DNA fragmentation. Our data support the concept that Vitamin D-3 compounds trigger apoptosis by mechanisms independent of estrogen signaling. These studies indicate that Vitamin D-3 based therapeutics may be beneficial, alone or in conjunction with other agents, for the treatment of estrogen independent breast cancer. (C) 2003 Elsevier Science Ltd. All rights reserved.