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，尤其是骨转移，是前列腺癌发病率和死亡率的最重要原因 患者因此，建立前列腺癌转移模型具有重要意义 描绘了这一过程的分子机制。 在我们的初步研究中，我们发现omega-3（n-3）多不饱和脂肪酸（PUFA）可以抑制 Pten基因敲除小鼠模型中前列腺癌的进展，并增加荷瘤小鼠的存活率 动物然而，没有评估n-3 PUFA对前列腺癌转移的影响。流行病学 数据表明，较高的鱼类消费量，丰富的n-3 PUFA来源， 降低转移性前列腺癌的风险。 在这个建议中，我们将开发一种自发性前列腺癌转移的动物模型，并使用这种模型。 模型以确定n-3 PUFA对转移的潜在作用。 目标1.建立一个定量的、可实时观察的前列腺癌转移模型。增强型黄色 荧光蛋白（EYFP）和lacZ标记物将用于肿瘤的实时监测和定量 分别在原发肿瘤部位和转移部位的负荷。转基因将是 将其引入前列腺特异性Pten敲除小鼠中， 癌症，从前列腺上皮内瘤变、原位癌、浸润癌到转移癌。的 EYFP和LacZ标记物将仅在前列腺肿瘤细胞中表达。重要的是，它们的表达水平 不会随着时间的推移或当前列腺肿瘤细胞转移到其他器官， 如骨头肺和淋巴结 目标2.确定饮食中补充n-3脂肪酸对前列腺癌转移的影响。 动物将喂食含有不同量n-3 PUFA的饲料。癌症的发展 将监测前列腺和肺、腹股沟淋巴结和胫骨/股骨中的转移。肿瘤负荷 将被量化。