Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice.
Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice.
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DOI：
10.3892/ijo.15.5.1011
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发表时间：
1999-11
影响因子：
5.2
通讯作者：
D. Rose;J. Connolly
中科院分区：
文献类型：
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作者：
D. Rose;J. Connolly
在含有4%亚油酸（LA，n-6 FA）的20%（wt/wt）脂肪饮食中添加4%的ω-3脂肪酸（n-3 FA）二十二碳六烯酸（DHA），可部分抑制MDA-MB-231人乳腺癌细胞系在无胸腺裸鼠中作为实体瘤的生长。这种减少的肿瘤生长与细胞增殖的显著抑制相关，如减少的Ki-67核增殖标记物表达和TUNEL阳性（凋亡）细胞的增加所示（均p<0.001）。补充DHA的饮食组小鼠的肿瘤中的微血管计数也减少（p<0.001），并且这种对血管生成的抑制与Ki-67表达的丧失正相关。肿瘤血管内皮细胞生长因子（VEGF）的浓度没有减少DHA喂养的小鼠。据推测，DHA在该乳腺癌模型中的抗血管生成性与我们证实的LA衍生的前列腺素E2、12-羟基二十碳四烯酸（12-HETE）和15-HETE合成的抑制有关，从而减少了这些已知的血管生成类二十烷酸对微血管内皮细胞的旁分泌刺激。
The addition of the omega-3 fatty acid (n-3 FA) docosahexaenoic acid (DHA), 4%, to a 20% (wt/wt) fat diet containing 4% linoleic acid (LA, n-6 FA) partially suppressed the growth of the MDA-MB-231 human breast cancer cell line as solid tumors in athymic nude mice. This reduced tumor growth was associated with significant inhibition of cell proliferation, as indicated by diminished Ki-67 nuclear proliferation marker expression, and an increase in TUNEL positive (apoptotic) cells (both p<0.001). The microvessel counts were also reduced in tumors from the DHA-supplemented dietary group of mice (p<0.001), and this suppression of angiogenesis was positively correlated with loss of Ki-67 expression. Tumor vascular endothelial cell growth factor (VEGF) concentrations were not reduced in the DHA-fed mice. It is postulated that the antiangiogenicity of DHA in this breast cancer model is related to our demonstrated inhibition of LA-derived prostaglandin E2, 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE synthesis, reducing the paracrine stimulation by these known angiogenic eicosanoids on microvessel endothelial cells.