A Chemoprotective Fish Oil- and Pectin-Containing Diet Temporally Alters Gene Expression Profiles in Exfoliated Rat Colonocytes throughout Oncogenesis
A Chemoprotective Fish Oil- and Pectin-Containing Diet Temporally Alters Gene Expression Profiles in Exfoliated Rat Colonocytes throughout Oncogenesis
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DOI：
10.3945/jn.110.134973
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
Lupton, Joanne R.
中科院分区：
文献类型：
--
作者：
Cho, Youngmi;Kim, Hyemee;Lupton, Joanne R.
我们已经证明，与玉米油和纤维素（CO/C）相比，含鱼油和果胶（FO/P）的饮食通过上调细胞凋亡和抑制增殖来预防结肠癌。为了阐明FO/P饮食诱导细胞凋亡和抑制肿瘤发生过程中的增殖的机制，我们分析了脱落的大鼠结肠细胞的时间基因表达谱。大鼠食用含FO/P或CO/C的饲料，并注射氧化偶氮甲烷（AOM; 2次，15 mg/kg体重，皮下注射）。在结肠癌的起始（AOM注射后24小时）和异常隐窝病灶（ACF）（注射后7周）和肿瘤（注射后128周）阶段收集的粪便用于多聚（A）+ RNA提取。使用代码连接阵列确定基因表达特征。测定表型（ACF、凋亡、增殖和肿瘤发生率）的变化，以建立有助于FO/P的化学保护作用的调节控制。与CO/C相比，在起始时，FO/P下调与细胞粘附有关的3个基因的表达，并增强凋亡。在ACF阶段，参与细胞周期调控的基因表达受到FO/P的调节，与CO/C大鼠相比，FO/P大鼠的增殖区缩小。与CO/C相比，FO/P还增加了肿瘤终点的凋亡和促进凋亡的基因表达。我们的结论是，化疗饮食对上皮细胞基因表达的影响可以在整个肿瘤发生过程中进行非侵入性监测，FO/P饮食具有化学保护作用，部分原因是它能够影响肿瘤发生的所有阶段中参与细胞凋亡和细胞周期调控的基因表达。J.营养141：1029-1035，2011.
We have demonstrated that fish oil- and pectin-containing (FO/P) diets protect against colon cancer compared with corn oil and cellulose (CO/C) by upregulating apoptosis and suppressing proliferation. To elucidate the mechanisms whereby FO/P diets induce apoptosis and suppress proliferation during the tumorigenic process, we analyzed the temporal gene expression profiles from exfoliated rat colonocytes. Rats consumed diets containing FO/P or CO/C and were injected with azoxymethane (AOM; 2 times, 15 mg/kg body weight, subcutaneously). Feces collected at initiation (24 h after AOM injection) and at aberrant crypt foci (ACF) (7 wk postinjection) and tumor 128 wk postinjection) stages of colon cancer were used for poly (A)+ RNA extraction. Gene expression signatures were determined using Code link arrays. Changes in phenotypes (ACF, apoptosis, proliferation, and tumor incidence) were measured to establish the regulatory controls contributing to the chemoprotective effects of FO/P. At initiation, FO/P downregulated the expression of 3 genes involved with cell adhesion and enhanced apoptosis compared with CO/C. At the ACF stage, the expression of genes involved in cell cycle regulation was modulated by FO/P and the zone of proliferation was reduced in FO/P rats compared with CO/C rats. FO/P also increased apoptosis and the expression of genes that promote apoptosis at the tumor endpoint compared with CO/C. We conclude that the effects of chemotherapeutic diets on epithelial cell gene expression can be monitored noninvasively throughout the tumorigenic process and that a FO/P diet is chemoprotective in part due to its ability to affect expression of genes involved in apoptosis and cell cycle regulation throughout all stages of tumorigenesis. J. Nutr. 141: 1029-1035, 2011.