Therapeutic Efficacy of Flaxseed in the Treatment of Ovarian Cancer

描述（申请人提供）：卵巢癌是妇科恶性肿瘤中最致命的一种，是妇女癌症死亡的第五大原因。卵巢癌的病因学知之甚少，没有合适的早期检测标记物。由于该疾病通常被诊断为晚期，存活率非常低，常规治疗方式或干预策略通常无效。多肉少菜的饮食可能与卵巢癌发病率的增加有关。欧米茄3（OM-3FA）和欧米茄6（OM-6FA）脂肪酸的不平衡导致癌症风险过高。研究表明，摄入大量OM-3FA的人群患乳腺癌、前列腺癌和结肠癌的发病率低于摄入较少OM-3FA的人群。因此，增加OM-3FA的消耗可能是预防卵巢癌、增强癌症治疗和显著延长寿命的无毒方式。亚麻籽是膳食纤维、OM-3FA α-亚麻酸（ALA）和植物雌激素木脂素的极好来源，这些物质是有效的抗雌激素，已被证明在某些癌症中具有抗增殖和促凋亡活性。一种有效的治疗或饮食干预，显着减少卵巢癌的进展有可能把卵巢癌变成一种疾病，妇女死亡与不从。拟议中的研究将测试富含亚麻籽的饮食在抑制卵巢癌方面的有效性，并使用蛋鸡作为卵巢癌模型来检查omega-3脂肪酸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可以模仿人类疾病。我们推测，亚麻籽丰富的饮食将导致显着降低卵巢癌的严重程度在蛋鸡。此外，我们假设亚麻籽的饮食干预由于ω-3脂肪酸和植物雌激素木脂素的协同作用而导致卵巢癌严重程度的改善。鉴定其表达受富含亚麻的饮食影响的分子靶点将提供对卵巢癌病因学的深入了解，并将为开发基于功能性食物的饮食干预以预防和治疗女性卵巢癌提供基础。基于三种试验饮食的创新使用提出了三个具体目标：常规亚麻籽vs.含高木酚素/低ω-3脂肪酸的亚麻籽（Linola）vs.亚麻籽油衍生的ω-3（高ω-3/低木酚素）。目的1）确定亚麻籽的最佳剂量;目的2）评估与常规亚麻籽相比，亚麻籽通过其降低含有高木脂素（Linola）或高ω-3（亚麻籽油）意志B的卵巢癌饮食的严重程度的机制;以及目的3）评估用这些饮食进行为期一年的饮食干预对老年产蛋鸡卵巢癌严重程度的功效。

DESCRIPTION (provided by applicant): Ovarian cancer is the most lethal of the gynecological malignacies and the 5th leading cause of cance death in women. The etiology of ovarian cancer is poorly understood and there are no suitable early detection markers. Due to the late stage at which the disease is usually diagnosed the survival rate is very low and conventional treatment modalities or intervention strategies are usually ineffective. A diet which is high in meats and low in vegetables may be corellated with increased 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. Flaxseed is an excellent source of dietary fiber, the OM-3FA alpha-linolenic acid (ALA), and phytoestrogen lignans, which are potent anti-estrogens that have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. An effective treatment or dietary intervention that significantly reduces the progression of ovarian cancer has the potential for turning ovarian cancer into a disease that women die WITH not from. The proposed studies will test the effectiveness of a flaxseed-enriched diet in the suppression of ovarian cancer, and examine the mechanism of action of omega-3 fatty acids 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 flaxseed enriched diet will cause a significant reduction in the severity of ovarian carcinoma in the laying hen. Furthermore, we hypothesize that dietary intervention with flaxseed results in amelioration of ovarian cancer severity due to the synergistic action of omega-3 fatty acids and phytoestrogen lignans. 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 based on the innovative used of three test diets: regular flaxseed vs. high lignan/low omega-3 fatty acid containing flaxseed (Linola) vs. flaxseed oil-derived omega-3 (high omega-3/low lignan). Aim 1) to determine the optimum dose of flaxseed; Aim 2) to evaluate the mechanism through which flaxseed reduces the severity of ovarian cancer diets containing either high lignan (Linola) or high omega-3(flaxseed oil) will b compared to regular flaxseed; and Aim 3) to evaluate the efficacy of one-year dietary intervention with these diet's on the severity of ovarian cancer in old laying hens.