Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis
Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis
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DOI：
10.1002/pros.20683
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发表时间：
2008-01-01
期刊：
影响因子：
2.8
通讯作者：
Isaacs, William B.
中科院分区：
文献类型：
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作者：
Freedland, Stephen J.;Mavropoulos, John;Isaacs, William B.
背景最近的证据表明，碳水化合物的摄入可能会影响前列腺癌的生物学。我们在异种移植模型中测试了无碳水化合物生酮饮食（NCKD）相对于西方饮食和低脂饮食是否会延迟前列腺癌的生长。75只雄性SCID小鼠喂食NCKD（84%脂肪-0%碳水化合物-16%蛋白质kcal）、低脂（12%脂肪-72%碳水化合物-16%蛋白质kcal）或西方饮食（40%脂肪-44%碳水化合物-16%蛋白质kcal）。低脂小鼠自由进食，其他臂通过改良的配对喂养方案进食。24天后，所有小鼠均注射LAPC-4细胞，并在肿瘤接近1，000 mm时处死（3）。尽管消耗相同的卡路里，但NCKD喂养的小鼠相对于低脂和西方饮食喂养的小鼠体重减轻（高达15%体重），并且需要额外的kcal来平衡体重。注射后51天，NCKD小鼠肿瘤体积比西方小鼠小33%（秩和，P = 0.009）。低脂肪和NCKD小鼠之间的肿瘤体积没有差异。饮食治疗与存活率显著相关（对数秩，P = 0.006），NCKD小鼠中存活时间最长，其次是低脂小鼠。NCKD小鼠血清IGFBP-3水平最高，IGF-1：IGFBP-3比值最低，而Western小鼠血清胰岛素和IGF-1水平最高。与其他组相比，NCKD小鼠的肝脏脂肪浸润显著减少。在这种异种移植模型中，尽管消耗更多的卡路里，但NCKD喂养的小鼠相对于西方小鼠显著降低了肿瘤生长并延长了生存期，并且与血清胰岛素和IGF轴激素相对于低脂或西方饮食的有利变化相关。
BACKGROUND. Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model.METHODS. Seventy-five male SCID mice were fed a NCKD (84% fat-0% carbohydrate-16% protein kcal), low-fat (12% fat-72% carbohydrate-16% protein kcal), or Western diet (40% fat-44% carbohydrate-16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm(3).RESULTS. Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P = 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms.CONCLUSIONS. In this xenograft model, despite consuming more calories, NCKD-fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet.