Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
Nutrients. 2022 May 12;14(10):2033. doi: 10.3390/nu14102033.
The relationship between colitis-associated colorectal cancer (CAC) and the dysregulation of iron metabolism has been implicated. However, studies on the influence of dietary iron deficiency on the incidence of CAC are limited. This study investigated the effects of dietary iron deficiency and dietary non-heme iron on CAC development in an azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model. The four-week-old mice were divided into the following groups: iron control (IC; 35 ppm iron/kg) + normal (NOR), IC + AOM/DSS, iron deficient (ID; <5 ppm iron/kg diet) + AOM/DSS, and iron overload (IOL; approximately 2000 ppm iron/kg) + AOM/DSS. The mice were fed the respective diets for 13 weeks, and the AOM/DSS model was established at week five. FTH1 expression increased in the mice’s colons in the IC + AOM/DSS group compared with that observed in the ID and IOL + AOM/DSS groups. The reduced number of colonic tumors in the ID + AOM/DSS and IOL + AOM/DSS groups was accompanied by the downregulated expression of cell proliferation regulators (PCNA, cyclin D1, and c-Myc). Iron overload inhibited the increase in the expression of NF-κB and its downstream inflammatory cytokines (IL-6, TNFα, iNOS, COX2, and IL-1β), likely due to the elevated expression of antioxidant genes (SOD1, TXN, GPX1, GPX4, CAT, HMOX1, and NQO1). ID + AOM/DSS may hinder tumor development in the AOM/DSS model by inhibiting the PI3K/AKT pathway by increasing the expression of Ndrg1. Our study suggests that ID and IOL diets suppress AOM/DSS-induced tumors and that long-term iron deficiency or overload may negate CAC progression.
结肠炎相关性结直肠癌（CAC）与铁代谢失调之间存在关联。然而，关于饮食铁缺乏对 CAC 发病率影响的研究有限。本研究在氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）小鼠模型中探讨了饮食铁缺乏和饮食非血红素铁对 CAC 发展的影响。将四周大的小鼠分为以下几组：铁对照组（IC；35 ppm 铁/公斤）+正常（NOR）、IC+AOM/DSS、缺铁组（ID；饮食中铁含量<5 ppm）+AOM/DSS 和铁过载组（IOL；约 2000 ppm 铁/公斤）+AOM/DSS。小鼠在各自的饮食中喂养 13 周，第五周建立 AOM/DSS 模型。与 ID 和 IOL+AOM/DSS 组相比，IC+AOM/DSS 组小鼠结肠中 FTH1 的表达增加。ID+AOM/DSS 和 IOL+AOM/DSS 组中结肠肿瘤数量减少伴随着细胞增殖调节剂（PCNA、cyclin D1 和 c-Myc）表达下调。铁过载抑制 NF-κB 及其下游炎症细胞因子（IL-6、TNFα、iNOS、COX2 和 IL-1β）表达增加，这可能是由于抗氧化基因（SOD1、TXN、GPX1、GPX4、CAT、HMOX1 和 NQO1）表达升高所致。ID+AOM/DSS 可能通过增加 Ndrg1 的表达来抑制 PI3K/AKT 通路，从而阻碍 AOM/DSS 模型中的肿瘤发展。本研究表明，ID 和 IOL 饮食抑制 AOM/DSS 诱导的肿瘤形成，长期铁缺乏或过载可能会阻止 CAC 进展。
