Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
Biol Reprod. 2013 May 16;88(5):121. doi: 10.1095/biolreprod.112.107276. Print 2013 May.
Pregnancy is a complex process that can be jeopardized when associated with cancer, because of the coexistence of two complex metabolic conditions: a fetus and cancer. The aim of this study was to evaluate fetal growth in association with cancer development as well as the indirect effects produced by tumors in pregnant mice subjected to a leucine-rich diet, knowing that leucine supplementation can minimize the tumor effects by acting as a cell signaling agent to improve the protein synthesis process. We evaluated fetuses (n = 6) from NMRI pregnant mice fed either a control or a leucine-rich diet in either the presence or absence of an MAC16 colon adenocarcinoma or ascitic fluid inoculation. The fetal serum amino acids were separated using high-performance liquid chromatography, and fetal cytokine levels were analyzed using a microsphere-based multiplex immunoassay (Luminex xMAP). Fetal body composition was measured as the water, fat, and protein total content and total serum protein, albumin, and glucose content. Tumor growth resulted in a severe reduction in fetal body weight and protein content and increased fetal resorption, associated with placental weight decrease; these effects were minimized by a leucine-rich diet. Serum total protein and glucose content were reduced in fetuses from tumor-bearing dams but were reverted by nutritional supplementation. The serum amino acid profiles differed significantly between the tumor-bearing mice fed with a leucine-rich diet and controls. Certain tumor effects were reproduced in fetuses from ascitic fluid-injected dams, suggesting indirect effects of tumor growth. We conclude that certain effects of tumor growth can be mimicked by ascitic fluid injection and can be modulated by a leucine-rich diet.
妊娠是一个复杂的过程，当与癌症同时存在时，会受到威胁，因为同时存在两种复杂的代谢情况：胎儿和癌症。本研究的目的是评估与癌症发展相关的胎儿生长情况，以及在接受富含亮氨酸饮食的怀孕小鼠中肿瘤产生的间接影响，因为亮氨酸补充可以通过作为细胞信号剂来最小化肿瘤的影响，从而改善蛋白质合成过程。我们评估了 NMRI 怀孕小鼠的胎儿（n = 6），这些小鼠分别喂食对照饮食或富含亮氨酸的饮食，同时存在或不存在 MAC16 结肠腺癌或腹水接种。使用高效液相色谱法分离胎儿血清氨基酸，并使用基于微球的多重免疫测定法（Luminex xMAP）分析胎儿细胞因子水平。胎儿体成分测量为水、脂肪和蛋白质总含量以及总血清蛋白、白蛋白和葡萄糖含量。肿瘤生长导致胎儿体重和蛋白质含量严重降低，并增加胎儿吸收，与胎盘重量减轻有关；富含亮氨酸的饮食可将这些影响降到最低。来自肿瘤荷瘤母鼠的胎儿血清总蛋白和葡萄糖含量降低，但通过营养补充得到恢复。与对照相比，富含亮氨酸饮食的荷瘤小鼠的血清氨基酸谱有显著差异。从注射腹水的母鼠的胎儿中重现了某些肿瘤作用，表明肿瘤生长的间接影响。我们得出结论，肿瘤生长的某些作用可以通过腹水注射来模拟，并可以通过富含亮氨酸的饮食来调节。
