Duke University Medical Center, Box 2626, Durham, NC 27710, USA.
Cancer Prev Res (Phila). 2010 Sep;3(9):1124-31. doi: 10.1158/1940-6207.CAPR-10-0071. Epub 2010 Aug 17.
Previous studies indicate that carbohydrate intake influences prostate cancer biology, as mice fed a no-carbohydrate ketogenic diet (NCKD) had significantly smaller xenograft tumors and longer survival than mice fed a Western diet. As it is nearly impossible for humans to consume and maintain NCKD, we determined whether diets containing 10% or 20% carbohydrate kcal showed similar tumor growth as NCKD. A total of 150 male severe combined immunodeficient mice were fed a Western diet ad libitum, injected with the human prostate cancer cell line LAPC-4, and then randomized 2 weeks later to one of three arms: NCKD, 10% carbohydrate, or 20% carbohydrate diets. Ten mice not injected were fed an ad libitum low-fat diet (12% fat kcal) serving as the reference in a modified-paired feeding protocol. Mice were sacrificed when tumors reached 1,000 mm(3). Despite consuming extra calories, all mice receiving low-carbohydrate diets were significantly lighter than those receiving a low-fat diet (P < 0.04). Among the low-carbohydrate arms, NCKD-fed mice were significantly lighter than the 10% or 20% carbohydrate groups (P < 0.05). Tumors were significantly larger in the 10% carbohydrate group on days 52 and 59 (P < 0.05), but at no other point during the study. Diet did not affect survival (P = 0.34). There were no differences in serum insulin-like growth factor-I or insulin-like growth factor binding protein-3 at sacrifice among the low-carbohydrate arms (P = 0.07 and P = 0.55, respectively). Insulin was significantly lower in the 20% carbohydrate arm (P = 0.03). LAPC-4 xenograft mice fed a low-carbohydrate diet (10-20% carbohydrate kcal) had similar survival as mice consuming NCKD (0% carbohydrate kcal).
先前的研究表明,碳水化合物的摄入量会影响前列腺癌的生物学特性,因为给予无碳水化合物生酮饮食(NCKD)的小鼠的异种移植肿瘤明显更小,且生存期长于给予西式饮食的小鼠。由于人类几乎不可能摄入并维持 NCKD,我们确定了含有 10%或 20%碳水化合物热量的饮食是否会表现出与 NCKD 相似的肿瘤生长。总共 150 只雄性严重联合免疫缺陷小鼠自由摄入西式饮食,注射人前列腺癌细胞系 LAPC-4,然后在 2 周后随机分为三组:NCKD、10%碳水化合物或 20%碳水化合物饮食。10 只未注射的小鼠自由摄入低脂肪饮食(12%脂肪热量),作为改良配对喂养方案中的参考。当肿瘤达到 1000mm3 时,处死小鼠。尽管摄入了额外的卡路里,但所有接受低碳水化合物饮食的小鼠都明显比接受低脂肪饮食的小鼠轻(P < 0.04)。在低碳水化合物组中,NCKD 喂养的小鼠比 10%或 20%碳水化合物组轻(P < 0.05)。在第 52 和 59 天,10%碳水化合物组的肿瘤明显更大(P < 0.05),但在研究的其他时间点则没有差异。饮食对生存没有影响(P = 0.34)。在低碳水化合物组中,在处死时,血清胰岛素样生长因子-I 或胰岛素样生长因子结合蛋白-3 没有差异(分别为 P = 0.07 和 P = 0.55)。20%碳水化合物组的胰岛素水平明显降低(P = 0.03)。给予低碳水化合物饮食(10-20%碳水化合物热量)的 LAPC-4 异种移植小鼠的生存情况与给予 NCKD(0%碳水化合物热量)的小鼠相似。