Rose D P, Connolly J M
Division of Nutrition and Endrocrinology, American Health Foundation, Valhalla, NY 10595, USA.
Nutr Cancer. 2000;37(2):119-27. doi: 10.1207/S15327914NC372_1.
Angiogenesis is a prerequisite for tumor growth and metastasis. Vascular endothelial cell proliferation, migration, and capillary formation are stimulated by angiogenic growth factors, which include the proteins vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor-beta, and eicosanoids synthesized from n-6 fatty acids. Clinical studies have shown that angiogenesis in solid tumors relates to a poor prognosis and, in premalignant lesions, indicates potential for cancerous transformation. High-fat, n-6 fatty acid-rich diets were associated with a relatively poor prognosis in breast cancer patients; in a nude mouse model the same diet enhanced breast cancer progression, whereas n-3 fatty acids exerted suppressive effects that were associated with impaired angiogenesis. Lipoxygenase and cyclooxygenase products of n-6 fatty acid metabolism are angiogenic in in vitro assays. This activity is blocked by pharmacological inhibitors of eicosanoid biosynthesis, and one, indomethacin, suppressed n-6 fatty acid-stimulated murine mammary carcinoma growth and metastasis and tumor vascularization. Review of the experimental data suggests that selective inhibitors of eicosanoid-synthesizing enzymes and dietary intervention with n-3 fatty acids merit clinical evaluation as adjuvant therapy and chemopreventive agents.
血管生成是肿瘤生长和转移的先决条件。血管生成生长因子可刺激血管内皮细胞增殖、迁移和毛细血管形成，这些因子包括血管内皮生长因子、碱性成纤维细胞生长因子和转化生长因子-β等蛋白质，以及由n-6脂肪酸合成的类花生酸。临床研究表明，实体瘤中的血管生成与预后不良相关，而在癌前病变中，则表明有癌变的可能性。高脂肪、富含n-6脂肪酸的饮食与乳腺癌患者相对较差的预后相关；在裸鼠模型中，相同的饮食会促进乳腺癌进展，而n-3脂肪酸则具有抑制作用，与血管生成受损有关。在体外试验中，n-6脂肪酸代谢的脂氧合酶和环氧化酶产物具有血管生成作用。类花生酸生物合成的药理抑制剂可阻断这种活性，其中一种抑制剂吲哚美辛可抑制n-6脂肪酸刺激的小鼠乳腺癌生长、转移和肿瘤血管形成。对实验数据的回顾表明，类花生酸合成酶的选择性抑制剂以及用n-3脂肪酸进行饮食干预作为辅助治疗和化学预防剂值得进行临床评估。
