Cruz Bread Leandro Gomes, da Silva Priscila Cristina, Tomasin Rebeka, Oliveira Andre Gustavo, Viana Lais Rosa, Salomao Emilianne Miguel, Gomes-Marcondes Maria Cristina Cintra
Department of Structural and Functional Biology, Biology Institute, State University of Campinas, UNICAMP, CP 6109, Campinas, São Paulo, 13083862, Brazil.
, Rua Monteiro Lobato, 255, Campinas, Zip code 13083862, Brazil.
BMC Cancer. 2016 Feb 4;16:58. doi: 10.1186/s12885-016-2103-x.
The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats.
Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20(th) day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits.
Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth.
孕期患癌合并了两种复杂且了解甚少的代谢和激素状况。这种关联会加重母亲和胎儿的病情。支链氨基酸亮氨酸可增强细胞活性，尤其是通过增加蛋白质合成来实现。本研究旨在分析富含亮氨酸的饮食对肿瘤直接和间接诱导的胎盘损伤的调节作用。这是通过评估从怀孕的荷瘤大鼠收集的胎盘组织中参与蛋白质合成和降解的基因表达，并测定抗氧化酶活性来完成的。
怀孕大鼠要么植入Walker 256肿瘤细胞，要么注射腹水（以研究肿瘤生长的间接影响），然后喂食富含亮氨酸的饮食。对照组的动物接受相同的程序，但喂食正常饮食。在怀孕第20天观察到肿瘤生长。喂食正常蛋白饮食的母鼠肿瘤生长最大。注射腹水模拟了肿瘤生长的影响。在喂食正常蛋白饮食的荷瘤组和注射腹水组中均观察到胎盘蛋白质合成减少和蛋白质降解增加。这些影响导致胎盘DNA和蛋白质含量降低以及脂质过氧化增加（通过丙二醛含量测定）。在肿瘤组中观察到胎盘蛋白质合成相关基因表达降低，同时编码与蛋白质降解相关蛋白和蛋白水解亚基的基因表达增加。
食用富含亮氨酸的饮食可抵消肿瘤生长和注射腹水所产生的影响。该饮食增强了细胞信号传导，改善了DNA和蛋白质含量的不足，并平衡了胎盘中蛋白质的合成和降解过程。细胞信号传导的改善包括mTOR/eIF途径的变化。总之，食用富含亮氨酸的饮食改善了荷瘤大鼠的胎盘代谢和细胞信号传导，这些变化减少了肿瘤生长所造成的有害影响。
