Sahin Kazim, Yenice Engin, Tuzcu Mehmet, Orhan Cemal, Mizrak Cengizhan, Ozercan Ibrahim H, Sahin Nurhan, Yilmaz Bahiddin, Bilir Birdal, Ozpolat Bulent, Kucuk Omer
Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey.
Poultry Research Institute, Ankara, Turkey.
J Cancer Prev. 2018 Mar;23(1):25-36. doi: 10.15430/JCP.2018.23.1.25. Epub 2018 Mar 30.
Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans.
In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected.
We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence ( < 0.01) as well as the number and the size of the tumors ( < 0.004 and < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes ( < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds ( < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues.
Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.
膳食中摄入番茄红素与卵巢癌风险降低有关，提示其对卵巢癌发生具有化学预防潜力。番茄红素在卵巢癌中的分子作用机制尚未完全明确。因此，在本研究中，我们使用蛋鸡模型来研究番茄红素对卵巢癌形成的影响，该模型是一种与人类自发卵巢癌发生具有生物学相关性的动物模型，因其发病率与人类相似。
本研究中，将150只102周龄的蛋鸡随机分为50只一组：一个对照组（每千克饲料含0毫克番茄红素）和两个处理组（每千克饲料含200毫克或400毫克番茄红素，即每只母鸡每天分别约摄入26毫克和52毫克）。在12个月末，采集血液、卵巢组织和肿瘤样本。
我们观察到，补充番茄红素显著降低了总体卵巢肿瘤发生率（<0.01）以及肿瘤的数量和大小（分别<0.004和<0.005）。番茄红素还显著降低了腺癌的发生率，包括浆液性和黏液性亚型（<0.006）。此外，我们还发现，与对照组相比，喂食番茄红素的母鸡血清中氧化应激标志物丙二醛水平显著降低（<0.001）。对卵巢肿瘤的分子分析显示，番茄红素降低了核因子κB的表达，同时增加了核因子红细胞2及其主要靶蛋白血红素加氧酶1的表达。此外，补充番茄红素通过诱导卵巢组织中活化STAT3的蛋白抑制剂表达，降低了STAT3的表达。
综上所述，我们的研究结果有力地支持了番茄红素通过抗氧化和抗炎机制对卵巢癌进行化学预防的潜力。
