Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice.
Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice.
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DOI：
10.1158/1940-6207.capr-15-0417
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Ronis M
中科院分区：
文献类型：
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作者：
Mercer KE;Pulliam C;Hennings L;Lai K;Cleves M;Jones E;Drake RR;Ronis M
在这项研究中，二乙基亚硝胺处理的雄性小鼠被分配到3组：35%高脂肪乙醇液体饮食（EtOH）与酪蛋白作为蛋白质来源，相同的EtOH液体饮食与大豆分离蛋白作为唯一的蛋白质来源（EtOH/SPI）和饲料组。EtOH喂养持续16周，正如预期的那样，与食物组相比，EtOH增加了嗜碱性病变和腺瘤的发生率和多样性，p<0.05。与EtOH和EtOH/SPI组相比，EtOH饮食中酪蛋白的大豆蛋白替代显著降低腺瘤进展，p<0.05。与EtOH组相比，EtOH/SPI组的肿瘤缩小对应于与肝脏肿瘤坏死因子α（Tnfα）和Cd 14抗原（Cd 14）表达减少以及NFκB1蛋白核积聚减少相关的肝损伤减轻（p<0.05）。使用高分辨率MALDI-FTICR成像质谱法检测鞘脂显示，EtOH组中长酰基链神经酰胺物质和鞘氨醇-1-磷酸（S1 P）的蓄积增加，而EtOH/SPI组中这些物质显著减少。慢性EtOH喂养还增加了β-连环蛋白转录靶点的mRNA表达，包括细胞周期蛋白D1（Ccnd 1）、基质金属肽酶7（Mmp 7）和谷氨酰胺合成酶（Glns），这些在EtOH/SPI组中降低，p<0.05。我们得出结论，大豆通过减少乙醇诱导的肝损伤引起的促炎和氧化环境，以及通过抑制β-连环蛋白信号传导减少肝细胞增殖来预防肿瘤发生。这些机制可能涉及鞘脂信号传导的变化。
In this study, diethylnitrosamine-treated male mice were assigned to 3 groups: a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/SPI) and a chow group. EtOH feeding continued for 16 wks. As expected, EtOH increased the incidence and multiplicity of basophilic lesions and adenomas compared to the chow group, p<0.05. Soy protein replacement of casein in the EtOH diet significantly reduced adenoma progression when compared to the EtOH and EtOH/SPI group, p<0.05. Tumor reduction in the EtOH/SPI group corresponded to reduced liver injury associated with decreased hepatic tumor necrosis factor α (Tnfα) and Cd14 antigen (Cd14) expression and decreased nuclear accumulation of NFκB1 protein compared to the EtOH group (p<0.05). Detection of sphingolipids using high resolution MALDI-FTICR Imaging mass spectrometry revealed increased accumulation of long acyl chain ceramide species, and sphingosine-1-phosphate (S1P) in the EtOH group that were significantly reduced in the EtOH/SPI group. Chronic EtOH feeding also increased mRNA expression of β-catenin transcriptional targets, including cyclin D1 (Ccnd1), matrix metallopeptidase 7 (Mmp7) and glutamine synthetase (Glns), which were reduced in the EtOH/SPI group, p<0.05. We conclude that soy prevents tumorigenesis by reducing pro-inflammatory and oxidative environment resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of β-catenin signaling. These mechanisms may involve changes in sphingolipid signaling.