The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer.
The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer.
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DOI：
10.1016/j.steroids.2012.06.005
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发表时间：
2012-09
期刊：
影响因子：
2.7
通讯作者：
Feldman D
中科院分区：
文献类型：
--
作者：
Krishnan AV;Swami S;Feldman D
骨化三醇（1,25-二羟基维生素D3）是维生素D的激素活性形式，可抑制包括乳腺癌（BCa）细胞在内的许多恶性细胞的生长。骨化三醇的抗癌作用机制包括：阻滞细胞周期、刺激细胞凋亡、抑制细胞的侵袭、转移和血管生成。此外，我们还发现了骨化三醇作用的新途径，特别是与抑制雌激素受体阳性（ER+） BCa细胞的生长有关。骨化三醇抑制COX-2的表达，增加15-PGDH的表达，从而降低炎性前列腺素（pg）的水平。我们的体外和体内研究表明，骨化三醇通过启动子II直接抑制芳香化酶的转录，以及通过启动子II间接降低芳香化酶转录的主要刺激因子pg的水平，从而降低BCa细胞和乳腺脂肪组织中选择性催化雌激素合成的芳香化酶的表达。骨化三醇下调ERα的表达，从而减弱BCa细胞中的雌激素信号，包括雌激素提供的增殖刺激。因此骨化三醇对雌激素合成和信号传导的抑制及其抗炎作用将在抑制ER+ BCa中发挥重要作用。我们假设，由于乳腺细胞中25-羟基维生素D-1α-羟化酶（CYP27B1）的存在，膳食维生素D会表现出类似的抗癌活性，从而确保循环的25-羟基维生素D在乳房微环境中局部转化为骨化三醇，并以旁分泌的方式抑制BCa的生长。细胞培养和小鼠体内数据强烈表明骨化三醇和膳食维生素D在预防和/或治疗女性ER+ BCa方面发挥有益作用。
Calcitriol (1,25-dihydroxyvitamin D3), the hormonally active form of vitamin D, inhibits the growth of many malignant cells including breast cancer (BCa) cells. The mechanisms of calcitriol anticancer actions include cell cycle arrest, stimulation of apoptosis and inhibition of invasion, metastasis and angiogenesis. In addition we have discovered new pathways of calcitriol action that are especially relevant in inhibiting the growth of estrogen receptor positive (ER+) BCa cells. Calcitriol suppresses COX-2 expression and increases that of 15-PGDH thereby reducing the levels of inflammatory prostaglandins (PGs). Our in vitro and in vivo studies show that calcitriol decreases the expression of aromatase, the enzyme that catalyzes estrogen synthesis selectively in BCa cells and in the mammary adipose tissue surrounding BCa, by a direct repression of aromatase transcription via promoter II as well as an indirect effect due to the reduction in the levels of PGs, which are major stimulator of aromatase transcription through promoter II. Calcitriol down-regulates the expression of ERα and thereby attenuates estrogen signaling in BCa cells including the proliferative stimulus provided by estrogens. Thus the inhibition of estrogen synthesis and signaling by calcitriol and its anti-inflammatory actions will play an important role in inhibiting ER+ BCa. We hypothesize that dietary vitamin D would exhibit similar anticancer activity due to the presence of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) in breast cells ensuring conversion of circulating 25-hydroxyvitamin D to calcitriol locally within the breast micro-environment where it can act in a paracrine manner to inhibit BCa growth. Cell culture and in vivo data in mice strongly suggest that calcitriol and dietary vitamin D would play a beneficial role in the prevention and/or treatment of ER+ BCa in women.
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DOI：
10.1016/s0960-0760(03)00028-1
发表时间：
2003-02-01
影响因子：
4.1
作者：
Flanagan, L;Packman, K;Welsh, J
通讯作者：
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影响因子：
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作者：
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影响因子：
4
作者：
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DOI：
10.1016/j.beem.2008.08.002
发表时间：
2008-08-01
影响因子：
7.4
作者：
Colston, Kay W.
通讯作者：
Colston, Kay W.
影响因子：
4.1
作者：
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