Department of Surgery, Durham Veterans Affairs Medical Center, Duke University School of Medicine, Durham, North Carolina, USA.
J Urol. 2010 Apr;183(4):1619-24. doi: 10.1016/j.juro.2009.12.003. Epub 2010 Feb 20.
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.
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 mm(3). 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.
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.
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.
先前的小鼠研究表明,低脂肪饮食会减缓前列腺癌的生长,而这些研究通常使用玉米油(ω-6)作为主要脂肪,而玉米油会促进前列腺癌的生长。我们之前使用基于饱和脂肪的饮食发现,在接受 LAPC-4 细胞异种移植的 SCID 小鼠(Taconic Farms,Hudson,New York)中,低脂肪和高脂肪饮食之间的肿瘤生长没有显著差异。在去势模型中是否会出现类似的结果尚不清楚。
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 200mm³时,将小鼠去势并随机分为等热量的西方饮食或低脂肪饮食(12%脂肪和 72%碳水化合物)。当肿瘤达到 1000mm³时,处死动物。收集血清并检测前列腺特异性抗原、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。检测肿瘤的总和磷酸化 Akt。
两组小鼠的体重相当。总体饮食组与生存无显著相关性(对数秩检验 p=0.32)。两组在前列腺特异性抗原(p=0.53)、胰岛素样生长因子轴参数(p>0.05)或磷酸化 Akt 与总 Akt 比值(p=0.22)方面均无统计学差异。
在本异种移植模型中,当脂肪来源为饱和脂肪时,我们未发现低脂肪与西方饮食喂养的小鼠之间的肿瘤生长或生存存在差异。这些结果与其他研究结果相矛盾,其他研究使用玉米油表明低脂肪饮食可延缓前列腺癌的生长,这表明脂肪类型在前列腺癌环境中可能与脂肪量同样重要。