Therapeutic Efficacy of Flax Seed in the Prevention of Ovarian Cancer

描述(申请人提供)：在美国，每年有超过24,000名女性被诊断出患有卵巢癌，其中一半死于卵巢癌。尽管在筛查和治疗方面取得了进展，但对潜在病因缺乏了解限制了预防策略。典型的西式饮食，多吃肉类，少吃蔬菜，可能与卵巢癌的发病率呈正相关。Omega 3(OM-3FA)和omega 6(OM-6FA)脂肪酸的不平衡导致了额外的癌症风险。研究表明，与摄入较少OM-3FA的人群相比，摄入大量OM-3FA的人群患乳腺癌、前列腺癌和结肠癌的几率更低。因此，增加OM-3FA的摄入量可能是预防卵巢癌、加强癌症治疗和显著延长生命的一种无毒方式。亚麻籽是膳食纤维、OM-3FAα-亚麻酸(ALA)以及木脂素的极好来源，木脂素是一种强大的抗雌激素，已被证明在某些癌症中具有抗增殖和促凋亡活性。这项研究将测试亚麻籽强化饲料的有效性，并以蛋鸡为卵巢癌模型，研究OM-3FA和肠雌激素的作用机制。除了衰老的母鸡，没有其他自发性上皮性卵巢癌的动物模型模仿人类的疾病。我们假设亚麻籽强化日粮可以降低蛋鸡卵巢癌的发病率。发现其表达受亚麻强化饮食影响的分子靶点将有助于深入了解卵巢癌的发病机制，并将为开展以功能食品为基础的饮食干预以防治女性卵巢癌奠定基础。提出了三个具体目标：1)确定母鸡日粮中添加亚麻籽降低卵巢癌发病率的有效剂量范围；2)确定亚麻籽日粮对卵巢癌相关炎症和前列腺素相关机制的影响；3)确定亚麻籽日粮对卵巢癌雌激素相关机制的影响。人们对使用OM-3FA降低癌症有相当大的兴趣，而HEN模型为研究饮食干预在预防卵巢癌中的效果提供了一个重要的机会。相关性：卵巢癌是一种高度致命的疾病，由于缺乏合适的动物模型，对卵巢癌的研究一直受到限制，因为除了产蛋母鸡外，没有其他动物会患上与女性相同类型的卵巢癌。以母鸡为模型，我们将研究omega-3/亚麻籽饮食作为预防卵巢癌的一种方法。

DESCRIPTION (provided by applicant): More than 24,000 women in the United States are diagnosed with ovarian cancer every year, and half of these women die from their disease. Despite advances in screening and treatment, the lack of understanding of the underlying etiology has limited prevention strategies. A typical Western diet, which is high in meats and low in vegetables, may be positively associated with ovarian cancer incidence. An imbalance of omega 3 (OM-3FA) and omega 6 (OM-6FA) fatty acids contributes to excess cancer risk. Studies indicate that populations that consume high amounts of OM-3FA have lower incidences of breast, prostate and colon cancers than do those that consume less OM-3FA. Thus increasing the consumption of OM-3FA may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. Flax seed is an excellent source of dietary fiber, the OM-3FA alpha-linolenic acid (ALA), as well as lignans, which are potent anti- estrogens that have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. The proposed studies will test the effectiveness of a flax seed enriched diet, and examine the mechanism of action of OM-3FA and enteroestrogens using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that a flax seed enriched diet will reduce the incidence of ovarian carcinoma in the laying hen. Identification of molecular targets whose expression is affected by flax enriched diet will provide insight into the etiology of ovarian cancer and will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women. Three Specific Aims are proposed: 1) Determine the effective dose range of flax seed added to the hen diet that reduces the incidence of ovarian cancer; 2) Determine the effect of flax seed diet on inflammation and prostaglandin- associated mechanisms involved in ovarian cancer; 3) Determine the effect of flax seed diet on estrogen- associated mechanism involved in ovarian cancer. There is considerable public interest in the use of OM-3FA to reduce cancer and the hen model provides an important opportunity to investigate the efficacy of dietary intervention in the prevention of ovarian cancer. Relevance: Research into ovarian cancer, a highly lethal disease, has been limited by the lack of suitable animal models, because, with the exception of the laying hen, no other animals are inflicted with the same type of ovarian cancer that affects women. Using the hen as our model we will investigate the use of omega-3/flax seed diet as a way to prevent ovarian cancer.