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，是女性癌症死亡的第五大原因。卵巢癌的病因知之甚少，也没有合适的早期检测标记物。由于该病通常被诊断为晚期，其存活率很低，常规治疗方式或干预策略通常无效。高肉类、低蔬菜的饮食可能与卵巢癌发病率的增加相关。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)和植物雌激素木脂素的极好来源，这些都是有效的抗雌激素，已被证明在某些癌症中具有抗增殖和促凋亡活性。有效的治疗或饮食干预可以显著减缓卵巢癌的进展，但有可能将卵巢癌转变为一种女性不会死于的疾病。这项拟议的研究将测试亚麻籽强化饮食在抑制卵巢癌方面的有效性，并以产蛋母鸡为卵巢癌模型，研究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模仿人类的疾病。我们假设，亚麻籽强化日粮将显著降低蛋鸡卵巢癌的严重程度。此外，我们假设，由于omega-3脂肪酸和植物雌激素木脂素的协同作用，亚麻籽饮食干预可以改善卵巢癌的严重程度。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。基于三种试验日粮的创新使用，提出了三个具体目标：普通亚麻籽与高木脂素/低omega-3脂肪酸亚麻籽(Linola)与亚麻籽油衍生的omega-3(高omega-3/低木脂素)。目的1)确定亚麻籽的最佳剂量；2)评价高木脂素(亚麻素)或高omega-3(亚麻籽油)日粮降低老年蛋鸡卵巢癌严重程度的机制；3)评价这些日粮对老年蛋鸡卵巢癌严重程度的干预效果。

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.