EFFECTS OF FATTY-ACIDS AND EICOSANOID SYNTHESIS INHIBITORS ON THE GROWTH OF 2 HUMAN PROSTATE-CANCER CELL-LINES
EFFECTS OF FATTY-ACIDS AND EICOSANOID SYNTHESIS INHIBITORS ON THE GROWTH OF 2 HUMAN PROSTATE-CANCER CELL-LINES
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DOI：
10.1002/pros.2990180306
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发表时间：
1991-01-01
期刊：
影响因子：
2.8
通讯作者：
CONNOLLY, JM
中科院分区：
文献类型：
--
作者：
ROSE, DP;CONNOLLY, JM
膳食脂肪酸（FAs）可能参与前列腺内的致癌过程并发展为临床表现的疾病。我们已经证明，在体外，亚油酸（一种omega-6多不饱和脂肪酸）的存在刺激了雄激素无反应的PC-3人前列腺癌细胞系的生长。在整个检测范围内（5-750 ng/ml），反应与FA浓度呈正相关。相反，鱼油中的两种omega-3脂肪酸二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）以剂量依赖性的方式抑制PC-3细胞的生长；两者同样有效，在浓度为2.0 μ g/ml时，生长减少约65% （P < 0.001）。同样对雄激素无反应的du145人前列腺癌细胞系对LA没有生长反应，并且在omega-3 FAs存在下培养时，对生长抑制的敏感性较低。吲哚美辛、艾斯维素和吡罗西康是类二十烷酸生物合成的药物抑制剂，它们具有不同的作用位点，其生长实验表明，人类前列腺癌细胞的生长需要白三烯和前列腺素生成的完整代谢途径。
Dietary fatty acids (FAs) may be involved in the carcinogenic process within the prostate gland and progression to clinically manifest disease. We have shown that growth of the androgen-unresponsive PC-3 human prostate cancer cell line is stimulated in vitro by the presence of linoleic acid (LA), an omega-6 polyunsaturated FA. The response was positively related to the FA concentration over the entire range examined (5-750 ng/ml). Conversely, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two omega-3 FAs present in fish oils, inhibited PC-3 cell growth in a dose-dependent manner; both were equally effective, with an approximately 65% reduction in growth occurring at a concentration of 2.0-mu-g/ml (P < 0.001). The DU 145 human prostate cancer cell line, which is also androgen-unresponsive, showed no growth response to LA and was less susceptible to growth inhibition when cultured in the presence of omega-3 FAs. Growth experiments with indomethacin, esculetin, and piroxicam, pharmacological inhibitors of eicosanoid biosynthesis with differing sites of action, indicated that human prostate cancer cell growth requires intact metabolic pathways for both leukotriene and prostaglandin production.