Effect of Dietary Omega-3 Fatty Acid Supplement on Prostate Cancer Metastasis

膳食 Omega-3 脂肪酸补充剂对前列腺癌转移的影响

• 批准号: 7393162
• 负责人: YONG Q CHEN
• 金额: $ 17.76万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7393162
• 关键词: Animal Model; Animals; Biological Assay; Cancer Patient; Carcinoma; Carcinoma in Situ; Clinical; Consumption; Data; Development; Diet; Eating; Fatty Acids; Femur; Fishes; Follow-Up Studies; Health Professional; Inguinal lymph node group; Invasive; Knock-out; Knockout Mice; Knowledge; LacZ Genes; Life; Lung; Malignant Neoplasms; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Modeling; Molecular; Monitor; Morbidity - disease rate; Neoplasm Metastasis; Omega-3 Fatty Acids; Organ; Primary Neoplasm; Process; Prospective Studies; Prostate; Prostatic Intraepithelial Neoplasias; Prostatic Neoplasms; Proteins; Relative Risks; Research Personnel; Risk; Site; Source; Time; Transgenes; Tumor Burden; Week; bone; feeding; lymph nodes; men; mortality; mouse model; neoplastic cell; programs; tibia; tumor; tumorigenesis

Metastasis, especially to the bone, is the most significant cause of morbidity and mortality in prostate cancer patients. Therefore, development of relevant metastasis models for prostate cancer is of critical importance for delineating the molecular mechanism underlining this process. In our preliminary studies, we showed that omega-3 (n-3) polyunstatured fatty acids (PUFAs) can inhibit the progression of prostate cancer in a Pten knockout mouse model, and increase survival of tumor-bearing animals. However, the effect of n-3 PUFA on prostate cancer metastasis was not assessed. Epidemiological data suggest that higher consumption of fish, a rich source of n-3 PUFA, is strongly associated with a reduced risk of metastatic prostate cancer. In this proposal, we will develop an animal model for spontaneous prostate cancer metastasis, and use this model to determine the potential effect of n-3 PUFA on metastasis. Aim 1. Develop a quantitative, live-observable model of prostate cancer metastasis. Enhanced yellow fluorescent protein (EYFP) and lacZ markers will be used for live-monitoring and quantification of tumor burden, respectively, at the primary tumor site and at the site of metastases. The transgenes will be introduced into prostate-specific Pten knockout mice that mimic well the clinical course of human prostate cancer, from prostatic intraepithelial neoplasia, carcinoma in situ, invasive carcinoma to metastasis. The EYFP and LacZ markers will be expressed only in prostate tumor cells. Importantly, their levels of expression will not be reduced or extinguished overtime or when prostate tumor cells metastasize to other organs such as the bone, lung, and lymph nodes. Aim 2. Determine the effect of dietary n-3 fatty acid supplement on prostate cancer metastasis. Animals will be fed with diets containing various amounts of n-3 PUFA. Development of cancer in the prostate and metastasis in the lung, inguinal lymph nodes and tibia/femur will be monitored. Tumor burden will be quantified.

转移，特别是对骨骼的转移，是前列腺癌发病和死亡率的最重要原因 患者。因此，开发针对前列腺癌的相关转移模型至关重要 用于描述强调此过程的分子机制。 在我们的初步研究中，我们表明omega-3（n-3）多舒张脂肪酸（PUFAS）可以抑制 在PTEN敲除小鼠模型中前列腺癌的进展，并增加肿瘤的存活率 动物。但是，未评估N-3 PUFA对前列腺癌转移的影响。流行病学 数据表明，较高的n-3 PUFA来源的鱼类消耗与 降低了转移性前列腺癌的风险。 在此提案中，我们将开发一种自发前列腺癌转移的动物模型，并使用此动物模型 确定N-3 PUFA对转移的潜在影响的模型。 目标1。开发一种定量的，可观察的前列腺癌转移模型。增强的黄色 荧光蛋白（EYFP）和LACZ标记将用于肿瘤的实时监测和定量 分别在原发性肿瘤部位和转移部位的负担。转基因将是 引入到前列腺特异性的PTEN敲除小鼠中，这些小鼠很好地模仿了人类前列腺的临床过程 癌症，从上皮内肿瘤，原位癌，浸润性癌到转移。这 EYFP和LACZ标记仅在前列腺肿瘤细胞中表达。重要的是，他们的表达水平 不会降低或熄灭加班或前列腺肿瘤细胞转移到其他器官时 作为骨骼，肺和淋巴结。 目标2。确定饮食N-3脂肪酸补充剂对前列腺癌转移的影响。 动物将饮食中含有各种数量的N-3 PUFA。癌症的发展 将监测肺，腹股沟淋巴结和胫骨/股骨的前列腺和转移。肿瘤负担 将被量化。