FATTY ACIDS AND HUMAN BREAST CANCER GROWTH

脂肪酸与人类乳腺癌的生长

• 批准号: 3197919
• 负责人: DAVID P ROSE
• 金额: $ 13.31万
• 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/3197919
• 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。 了解不同因素的影响 FAs 类型对人乳腺癌细胞生物学行为的影响 对于合理制定疾病饮食干预措施至关重要 预防，以及手术后的辅助治疗。 为此，提出了利用裸鼠模型进行一系列研究 用于人类乳腺癌细胞转移。 这些都会比较效果 含有不同水平和比例的 n-6 和 n-3 的饲料 FA 对 MDA-MB-435 细胞在原代（接种）位点和上表面生长的影响 转移。 机理研究将重点关注 (a) n-6 的作用 FA 衍生的类二十烷酸在调节肿瘤细胞生长和表达中的作用 转移潜能，以及 (b) 肌醇磷脂信号 转导途径。 将检测前列腺素和白三烯 直接在实体瘤中进行，并使用 [14C] 标记的 n-6 FA 来评估 它们掺入再培养的原代细胞和 转移细胞，随后花生四烯酸的动员及其 用于类二十烷酸生产。 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 来自原发性和转移性肿瘤的细胞，这些细胞是在小鼠体内发育而来的 各种饮食群体。