Effect of altering dietary ω-6/ω-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2
Effect of altering dietary ω-6/ω-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2
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DOI：
10.1158/1078-0432.ccr-06-0459
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发表时间：
2006-08-01
影响因子：
11.5
通讯作者：
Aronson, William J.
中科院分区：
文献类型：
--
作者：
Kobayashi, Naoko;Barnard, R. James;Aronson, William J.
目的：确定改变膳食中omega-6(n-6)-3(n-3)多不饱和脂肪酸的含量是否影响雄激素敏感型前列腺癌移植瘤的生长、肿瘤膜脂肪酸组成、肿瘤环氧合酶-2和前列腺素E-2(PGE(2))水平。实验设计：以n-6脂肪酸为主的脂肪(n-6组)和n-6和n-3脂肪酸组成的脂肪(n-3组)按1：1的比例喂饲等热量的雄性联合免疫缺陷小鼠。并注射了S.C.与洛杉矶前列腺癌4(LAPC-4)细胞。每周测量肿瘤体积和小鼠体重，每周测量卡路里摄入量，并在注射后8周采集肿瘤和血清。结果：与n-6组相比，n-3组的肿瘤生长率、最终肿瘤体积和血清前列腺特异性抗原水平均降低。N-3组肿瘤细胞增殖减少(Ki67染色)，细胞凋亡增加(末端核苷酸转移酶介导的缺口末端标记染色)。在含n-3组血清的培养液中，LAPC-4细胞的体外增殖较含n-6组血清的LAPC-4细胞低22%。血清和肿瘤膜中n-6/n-3脂肪酸比值n-3组低于n-6组。此外，n-3组肿瘤环氧合酶-2蛋白和mRNA水平降低，前列腺素E(2)水平降低83%，血管内皮生长因子表达降低。结论：这些结果为临床试验评估来自鱼油的n-3脂肪酸对前列腺癌男性患者肿瘤PGE(2)和膜脂肪酸组成、血清和肿瘤进展的生物标志物的影响提供了可靠的基础。
Purpose: To determine whether altering the dietary content of omega-6 (n-6) ando)-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E-2 (PGE(2)) levels.Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection.Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE(2) levels, and decreased vascular endothelial growth factor expression.Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2) and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.