Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture.

Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture.
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发表时间:
1990-11
期刊:
影响因子:
11.2
通讯作者:
D. Rose;J. Connolly
D. Rose;J. Connolly
中科院分区:
医学1区
文献类型:
--
作者:
D. Rose;J. Connolly

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饮食中的脂质可能影响乳腺癌的进展和预后。用MDA-MB-231人乳腺癌细胞系研究了不同种类的游离脂肪酸(FAs)在无血清培养基中对生长的直接影响以及参与类二十烷生物合成。亚油酸(一种omega - 6 FA)刺激MDA-MB-231细胞生长,浓度为0.75微克/毫升时效果最佳,而油酸(一种omega - 9 FA)在0.25微克/毫升时产生生长刺激,但浓度更高时产生抑制作用。二十二碳六烯酸在0.5 ~ 2.5微克/毫升浓度范围内对细胞生长表现出剂量相关的抑制作用;二十碳五烯酸,也是一种omega - 3脂肪酸,效果较差。饱和脂肪酸也有类似的抑制作用。吲哚美辛在高浓度时是环加氧酶和脂加氧酶催化的类二十烷合成途径的抑制剂,当亚油酸浓度为40微克/毫升时,可抑制最佳剂量的细胞生长刺激。用吡罗昔康、去二氢愈木酸和esculetin等类二十烷类生物合成抑制剂对前列腺素和白三烯途径酶的选择性不同进行的实验表明,MDA-MB-231细胞的生长依赖于白三烯而不是前列腺素的产生。
Dietary lipids may influence breast cancer progression and prognosis. The MDA-MB-231 human breast cancer cell line was used to examine the direct effects of the various classes of free fatty acids (FAs) on growth in serum-free medium and the involvement of eicosanoid biosynthesis. Linoleic acid, an omega 6 FA, stimulated MDA-MB-231 cell growth with an optimal effect at a concentration of 0.75 microgram/ml, whereas oleic acid, an omega 9 FA, produced growth stimulation at 0.25 microgram/ml but was inhibitory at higher concentrations. Docosahexaenoic acid exhibited a dose-related inhibition of cell growth at concentrations ranging from 0.5 to 2.5 micrograms/ml; eicosapentaenoic acid, also an omega 3 FA, was less effective. Similar inhibitory effects occurred with saturated FAs. Indomethacin, which at high concentrations is an inhibitor of both the cyclooxygenase- and lipoxygenase-catalyzed pathways of eicosanoid synthesis, suppressed cell growth stimulation by an otherwise optimal dose of linoleic acid when present at 40 micrograms/ml. Experiments with piroxicam, nordihydroguaiaretic acid, and esculetin, other inhibitors of eicosanoid biosynthesis with varying selectivity for enzymes of the prostaglandin and leukotriene pathways, indicated that MDA-MB-231 cell growth was dependent on leukotriene rather than prostaglandin production.