Interactive Effects of Flaxseed and Tamoxifen in Breast*

亚麻籽和他莫昔芬对乳房的相互作用*

• 批准号: 6791441
• 负责人: Lilian Umale Thompson
• 金额: $ 8.1万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-18 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791441
• 关键词: MCF7 cell; athymic mouse; breast neoplasms; combination cancer therapy; dietary supplements; dosage; drug screening /evaluation; estrogen receptors; gas chromatography mass spectrometry; growth factor; immunocytochemistry; neoplasm /cancer chemotherapy; neoplasm /cancer nutrition therapy; neoplastic growth; nutrient drug interaction; nutrition related tag; phytoestrogens; tamoxifen; terminal nick end labeling; western blottings

DESCRIPTION (provided by applicant): Tamoxifen (TAM) is an adjuvant therapy for women with estrogen receptor (ER) (+) breast cancer, acting as an estrogen antagonist. Women taking TAM report the use of complementary dietary supplements including phytoestrogen-rich foods such as soy and flaxseed to reduce tumor growth and recurrence and TAM-induced menopausal symptoms. However, the interactive effects of TAM and flaxseed on ER(+) breast cancer has not been tested in animal or human models. Therefore the long term objective of this study is to determine whether flaxseed can enhance the tumor inhibitory effect of TAM in both premenopausal and postmenopausal women. The specific aims are: (1) to determine the effect of flaxseed and TAM, alone and in combination, on the growth of human ER(+) breast cancer (i.e. MCF-7), in the presence of high or low concentrations of estrogen and (2) to determine some of the mechanisms. The study plan is to inject ovariectomized athymic mice with MCF-7 cells, implant them with a pellet containing 1.7 mg estradiol (E2), and then feed them with basal diet (BD). In Experiment 1, at week 5 when the tumors are already established, the E2 pellet will be removed and replaced by a new one (to simulate high E2 levels in premenopausal women). The mice will then be randomized into 7 groups such that they have similar mean tumor size: Groups 1, 4 and 7 will be fed the BD, Groups 2 and 5, the 5 % flaxseed, groups 3 and 6, the 10% flaxseed. Groups 4, 5 and 6 will also receive an implant of TAM (5 mg) pellet. Group 7 will not have E2 replaced (negative control). In Experiment 2, the plan is the same as in Experiment 1 except that at week 5, the existing E2 pellet will be removed from all mice (to simulate low E2 levels in postmenopausal women) before randomization to 7 groups. Group 7 will have the E2 replaced (positive control). In both experiments, palpable tumors will be measured weekly and at week 20, will be excised for analysis to explore potential mechanisms, including cell proliferation, apoptosis, angiogenesis, expression of ER and growth factors.

说明(申请人提供)：他莫昔芬()是一种治疗雌激素受体(ER)(+)乳腺癌女性的辅助疗法，作为雌激素拮抗剂。服用的妇女报告说，她们使用辅助性膳食补充剂，包括富含植物雌激素的食物，如大豆和亚麻籽，以减少肿瘤的生长和复发，以及引发的更年期症状。然而，和亚麻籽对ER(+)乳腺癌的交互作用尚未在动物或人类模型中进行测试。因此，本研究的长期目标是确定亚麻籽是否能增强对绝经前和绝经后妇女的抑瘤作用。其具体目的是：(1)确定亚麻籽和单独或联合在高或低浓度雌激素存在下对人ER(+)乳腺癌(即MCF-7)生长的影响；(2)探讨其作用机制。研究计划是给去卵巢的裸鼠注射MCF-7细胞，植入含有1.7 mg雌二醇的颗粒，然后用基础饲料(BD)喂养它们。在实验1中，在肿瘤已经建立的第5周，E2颗粒将被移除，并被新的颗粒取代(以模拟绝经前妇女的高E2水平)。然后将小鼠随机分为7组，使它们的平均肿瘤大小相似：1、4和7组将喂饲BD，2和5组，5%亚麻籽，3和6组，10%亚麻籽。第4、5、6组还将植入颗粒(5 Mg)。第7组不替换E2(阴性对照)。在实验2中，计划与实验1相同，只是在第5周，在随机分成7组之前，从所有小鼠身上取出现有的E2颗粒(以模拟绝经后妇女的低E2水平)。第7组更换雌二醇组(阳性对照)。在这两个实验中，每周都会测量可触及的肿瘤，并在第20周切除肿瘤进行分析，以探索潜在的机制，包括细胞增殖、凋亡、血管生成、ER和生长因子的表达。