FATTY ACIDS AND HUMAN BREAST CANCER GROWTH

脂肪酸与人类乳腺癌的生长

• 批准号: 3197918
• 负责人: DAVID P ROSE
• 金额: $ 12.67万
• 依托单位: INSTITUTE FOR CANCER PREVENTION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3197918
• 关键词: arachidonate; athymic mouse; biological signal transduction; breast neoplasms; cell membrane; dietary lipid; disease /disorder model; eicosanoid metabolism; eicosanoids; enzyme activity; fatty acid biosynthesis; fatty acids; indomethacin; inositol; leukotrienes; linoleate; metastasis; nutrition related tag; omega 3 fatty acid; phospholipase A2; phospholipase C; phospholipids; prostaglandins; protein kinase C; thin layer chromatography; tissue /cell culture; vegetable oils

Evidence from animal models and experimental human breast cancer cell growth in nude mice indicates that omega-6 fatty acids (n-6 FAs) stimulate growth and metastasis of mammary cancer, whereas omega-3 (n-3) FAs may exert an inhibitory effect. An understanding of the influence of different types of FAs on the biological behavior of human breast cancer cells is essential for the rational development of dietary interventions for disease prevention, and as adjuvant therapy after surgery. To this end, a series of studies is proposed utilizing a nude mouse model for human breast cancer cell metastasis. These will compare the effects of feeding diets containing different levels and proportions of n-6 and n-3 FAs on MDA-MB-435 cell growth at the primary (inoculation) site and on metastasis. Mechanistic studies will focus on (a) the role of the n-6 FA-derived eicosanoids in modulating tumor cell growth and expression of metastatic potential, and (b) on the inositol phospholipid signal transduction pathway. Prostaglandin and leukotrienes will be assayed directly in solid tumors, and [14C]-labelled n-6 FAs employed to assess their incorporation into membrane phospholipids of recultured primary and metastatic cells, the subsequent mobilization of arachidonate, and its utilization for eicosanoid production. The rates of inositol phospholipid hydrolysis, diacylglycerol production, and phospholipase C and protein kinase C Activities will be compared in cells from primary and metastatic tumors, which developed in mice from the various dietary groups.

来自动物模型和实验性人类乳腺癌细胞的证据 裸鼠的生长表明omega-6脂肪酸(n-6 FA)刺激 乳腺癌的生长和转移，而omega-3(n-3)FA可能 发挥抑制作用。对不同因素影响的理解 不同类型的脂肪酸对人乳腺癌细胞生物学行为的影响 对合理制定针对疾病的饮食干预措施至关重要 预防，并作为术后的辅助治疗。 为此，提出了一系列利用裸鼠模型的研究 用于人类乳腺癌细胞的转移。这些将比较效果 饲喂含有不同水平和比例的n-6和n-3的日粮 Fas对MDA-MB-435细胞在原代(接种)部位和接种部位生长的影响 转移。机械论研究将集中于(A)n-6的作用 脂肪酸衍生二十烷类化合物对肿瘤细胞生长及相关基因表达的影响 转移潜能，以及(B)肌醇磷脂信号 转导途径。前列腺素和白三烯将被检测 直接在实体肿瘤中，和[14C]标记的n-6 FA用于评估 它们被掺入原代和再培养的细胞膜磷脂中 转移细胞，随后花生四烯酸的动员，及其 用于二十烷类化合物生产的利用。 肌醇磷脂水解率、二酰甘油生成率、 磷脂酶C和蛋白激酶C的活性将在 来自原发和转移肿瘤的细胞，这些细胞是从小鼠体内发展而来的 不同的饮食群体。