FATTY ACIDS AND HUMAN BREAST CANCER GROWTH

来自动物模型和实验性人乳腺癌细胞的证据 裸鼠的生长表明ω-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。 了解不同的影响 FAs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，并作为手术后的辅助治疗。 为此，提出了利用裸鼠模型的一系列研究 for human人breast乳腺癌cell细胞metastasis转移. 这些会比较 饲喂含有不同水平和比例的n-6和n-3的日粮 FA对原代（接种）部位MDA-MB-435细胞生长和 转移 机制研究将集中在（a）n-6的作用 FA衍生的类二十烷酸调节肿瘤细胞生长和表达 转移潜能，和（B）肌醇磷脂信号 转导途径 将测定前列腺素和白三烯 直接在实体瘤中，[14 C]标记的n-6 FA用于评估 将它们掺入再培养的原代和 转移细胞，随后的花生四烯酸动员，及其 用于类花生酸生产。 肌醇磷脂水解率，甘油二酯生成率， 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，这些细胞在小鼠中发育， 不同的饮食群体。

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.