Huang Y C, Jessup J M, Forse R A, Flickner S, Pleskow D, Anastopoulos H T, Ritter V, Blackburn G L
Cancer Research Institute, Deaconess Pathway Health Network, Department of Surgery, Harvard Medical School, Boston, Massachusetts 02215, USA.
Lipids. 1996 Mar;31 Suppl:S313-7. doi: 10.1007/BF02637099.
The n-3 fatty acids (C20:5, eicosapentaenoic acid; c22:6, docosahexaenoic acid) may be important in the development, growth, and metastasis of colon cancer, a leading cause of death in North America. Patients who have had a bowel neoplasm have a high risk of developing a second neoplasm, and this risk is associated with a high percentage of cells correspond to the S phase of bromodeoxyuridine (BrdUrd) labeling in mucosal epithelial cells. To determine the effect of n-3 fatty acid supplementation on DNA synthesis of rectal mucosa, patients with stage 1 or stage 2 colon carcinoma or adenomatous polyps were randomized to consume either 9 g/d n-3 fatty acid capsules or 9 g/d placebo capsules. Plasma phospholipid fatty acid analysis and proctoscopic mucosal biopsies were performed at baseline, 3, and 6 mon. Colonic crypts were isolated from the mucosa, disassociated with enzymes, and incubated with BrdUrd, and %S phase was measured by flow cytometry. The plasma phospholipid n-6/n-3 ratio was determined by gas chromatography. Supplement compliance was assessed by plasma phospholipid n-6/n-3 ratio. Mean capsule consumption in these two group was 82%. Prior to supplementation, there were no significant differences in the %S phase and the plasma n-6/n-3 ratio between these groups. Patients whose colonic epithelial cells indicated hyperproliferation at baseline showed a strongly positive correlation to the %S phase of BrdUrd uptake and the n-6/n-3 ratio. There was no significant change after n-3 treatment in patients with low baseline. Those in the placebo group showed no significant difference in n-6/n-3 ratio, although there was an increase in the %S phase of BrdUrd uptake at 6 mon. The n-3 group did not have significant side effects, and polyps were not found after completing 12 mon of n-3 fatty acid supplementation. This study suggests that n-3 fatty acid may be a useful chemopreventive agent in some patients as reflected in a plasma biomarker of colon tumor growth and metastasis. A low plasma phospholipid n-6/n-3 fatty acid ratio may serve as a nutritional marker that is associated with colonic epithelial cell hyperproliferation in the n-3-supplemented group as compared with the placebo group. Characteristics of mucosal proliferation at baseline may be a crucial factor for the effect of n-3 fatty acid supplementation.
n-3脂肪酸（二十碳五烯酸，C20:5；二十二碳六烯酸，C22:6）在结肠癌的发生、发展及转移过程中可能具有重要作用，结肠癌是北美地区主要的致死原因之一。患有肠道肿瘤的患者发生第二种肿瘤的风险较高，且这种风险与黏膜上皮细胞中对应于溴脱氧尿苷（BrdUrd）标记S期的细胞比例较高有关。为了确定补充n-3脂肪酸对直肠黏膜DNA合成的影响，将患有1期或2期结肠癌或腺瘤性息肉的患者随机分为两组，分别服用9克/天的n-3脂肪酸胶囊或9克/天的安慰剂胶囊。在基线、3个月和6个月时进行血浆磷脂脂肪酸分析和直肠镜黏膜活检。从黏膜中分离出结肠隐窝，用酶解离后与BrdUrd一起孵育，通过流式细胞术测量S期百分比。通过气相色谱法测定血浆磷脂n-6/n-3比值。通过血浆磷脂n-6/n-3比值评估补充剂依从性。这两组的平均胶囊服用量为82%。在补充之前，两组之间的S期百分比和血浆n-6/n-3比值没有显著差异。基线时结肠上皮细胞显示增殖过度的患者，其BrdUrd摄取的S期百分比与n-6/n-3比值呈强正相关。基线水平较低的患者在接受n-3治疗后没有显著变化。安慰剂组的n-6/n-3比值没有显著差异，尽管在6个月时BrdUrd摄取的S期百分比有所增加。n-3组没有明显的副作用，在完成12个月的n-3脂肪酸补充后未发现息肉。这项研究表明，n-3脂肪酸在某些患者中可能是一种有用的化学预防剂，这在结肠肿瘤生长和转移的血浆生物标志物中得到了体现。与安慰剂组相比，血浆磷脂n-6/n-3脂肪酸比值较低可能作为一种营养标志物，与补充n-3组的结肠上皮细胞增殖过度有关。基线时黏膜增殖的特征可能是n-3脂肪酸补充效果的关键因素。
