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

转移，尤其是转移到骨，是前列腺癌发病率和死亡率的最重要原因。 病人。因此，前列腺癌相关转移模型的建立具有重要意义。 来描述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(PUFAs)可以抑制 前列腺癌在Pten基因敲除小鼠模型中的进展和提高荷瘤小鼠的存活率 动物。然而，n-3多不饱和脂肪酸在前列腺癌转移中的作用尚未得到评估。流行病学 数据表明，更高的鱼类消费量，n-3多不饱和脂肪酸的丰富来源，与 降低转移性前列腺癌的风险。 在这项提案中，我们将建立一种前列腺癌自发转移的动物模型，并使用 模型以确定n-3多不饱和脂肪酸在转移中的潜在作用。 目的1.建立前列腺癌转移的定量、活体观察模型。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量化 负荷分别位于原发肿瘤部位和转移部位。转基因将是 引入前列腺特异性Pten基因敲除小鼠，很好地模拟了人类前列腺的临床过程 癌症，从前列腺上皮内瘤变、原位癌、浸润性癌到转移。这个 EYFP和LacZ标记物将只在前列腺肿瘤细胞中表达。重要的是，他们的表达水平 不会随着时间的推移而减少或熄灭，或者当前列腺肿瘤细胞转移到其他器官时 如骨、肺和淋巴结节。 目的2.探讨饮食中补充n-3脂肪酸对前列腺癌转移的影响。 动物将被喂以含有不同数量的n-3多不饱和脂肪酸的饲料。癌症在中国的发展 将监测前列腺癌和肺、腹股沟淋巴结和胫骨/股骨的转移。肿瘤负担 将会被量化。

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.