Effect of Isocaloric Low Fat Diet on Prostate Cancer Xenograft Progression in a Hormone Deprivation Model

Effect of Isocaloric Low Fat Diet on Prostate Cancer Xenograft Progression in a Hormone Deprivation Model
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DOI:
10.1016/j.juro.2009.12.003
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发表时间:
2010-04-01
期刊:
影响因子:
6.6
通讯作者:
Freedland, Stephen J.
Freedland, Stephen J.
中科院分区:
医学1区
文献类型:
--
作者:
Lloyd, Jessica C.;Antonelli, Jodi A.;Freedland, Stephen J.

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目的:以前的小鼠研究表明,低脂肪饮食可以减缓前列腺癌的生长,通常使用玉米油(omega-6)作为主要脂肪,它可以促进前列腺癌的生长。使用基于饱和脂肪的饮食,我们先前发现用LAPC-4细胞异种移植的低脂肪和高脂肪喂养的SCID小鼠(Taconic Farms,哈德逊,纽约)之间的肿瘤生长没有显著差异。材料和方法:共80只雄性SCID小鼠喂食西方饮食(40%脂肪和44%碳水化合物),并注射LAPC-4人前列腺癌细胞。当肿瘤达到200 mm(3)时,将小鼠阉割,并随机分配至等热量的西方或低脂饮食(12%脂肪和72%碳水化合物)。当肿瘤为1,000 mm 3时处死动物。收集血清并测定前列腺特异性抗原、胰岛素、胰岛素样生长因子1和胰岛素样生长因子结合蛋白3。肿瘤测定总Akt和磷酸化Akt.Results:小鼠体重在2组是相等的。总体饮食组与生存率无显著相关性(对数秩p = 0.32)。在处死时,两组之间的前列腺特异性抗原(p = 0.53)、胰岛素样生长因子轴参数(每个p >0.05)或p-Akt-to-t-Akt比率(p = 0.22)没有统计学显著差异。这些结果与其他研究相冲突,在这些研究中,玉米油被用来表明低脂饮食可以延缓前列腺癌的生长,这表明脂肪类型可能与前列腺癌中的脂肪量一样重要。
Purpose: Previous mouse studies suggesting that low fat diets slow prostate cancer growth often used corn oil (omega-6), which enhances prostate cancer growth, as the primary fat. Using a saturated fat based diet we previously found no significant difference in tumor growth between low and high fat fed SCID mice (Taconic Farms, Hudson, New York) xenografted with LAPC-4 cells. Whether similar results would hold in a castration model is unclear.Materials and Methods: A total of 80 male SCID mice were fed a Western diet (40% fat and 44% carbohydrate) and injected with LAPC-4 human prostate cancer cells. When tumors were 200 mm(3), the mice were castrated and randomized to an isocaloric Western or a low fat diet (12% fat and 72% carbohydrate). Animals were sacrificed when tumors were 1,000 mm3. Serum was collected and assayed for prostate specific antigen, insulin, insulin-like growth factor 1 and insulin-like growth factor binding protein 3. Tumors were assayed for total and phosphorylated Akt.Results: Mouse weight was equivalent in the 2 groups. Overall dietary group was not significantly associated with survival (log rank p = 0.32). There were no statistically significant differences in prostate specific antigen (p = 0.53), insulin-like growth factor axis parameters (each p >0.05) or p-Akt-to-t-Akt ratios (p = 0.22) between the groups at sacrifice.Conclusions: In this xenograft model we found no difference in tumor growth or survival between low fat vs Western fed mice when the fat source was saturated fat. These results conflict with those of other studies in which corn oil was used to show that low fat diets delay prostate cancer growth, suggesting that fat type may be as important as fat amount in the prostate cancer setting.