膳食血红素铁促进结直肠癌变机制初探  

A preliminary study on the mechanism of dietary heme in promoting colorectal cancer

作　　者：陈宣承 李红领 李海涛[1] CHEN Xuancheng;LI Hongling;LI Haitao(School of Food Science and Technology,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学食品学院,江苏无锡214122

出　　处：《食品与发酵工业》2022年第1期91-97,共7页Food and Fermentation Industries

基　　金：国家自然科学基金资助项目(31972973,81773064)。

摘　　要：流行病学研究揭示红肉摄入过多增加结直肠癌的发生风险,但机制未明。血红素铁是一种广泛存在于动物红肉、肝脏、血液中的有机铁,为探究红肉摄入对结直肠癌肿瘤发生及增殖的影响,并进一步解析作用机制。该文建立原发结直肠癌肿瘤小鼠模型,发现在血红素铁的干预下,能够显著增加氧化应激及结直肠癌肿瘤的发生发展程度;通过蛋白质印迹法分析,在动物模型的结肠组织中,血红素铁刺激结直肠癌肿瘤小鼠,黄嘌呤氧化酶(xanthine oxidase,XOD)、p-H2AX及p-STAT3表达量均会上调,同时肿瘤组织较瘤旁组织表达更为明显,通过细胞实验发现,在一定剂量的蔗糖铁和脂多糖的共同作用下可以上调经佛波酯诱导THP-1细胞分化成的巨噬细胞XOD的表达量;通过免疫组化实验发现,在小鼠结肠部位中XOD的表达位置和巨噬细胞表达位置相重合。结论显示,血红素铁会增加结直肠癌肿瘤小鼠的肿瘤发生及发展程度,且此现象与XOD表达上调有关。Epidemiological study has revealed that excessive intake of red meat could increase the risk of colorectal cancer,but the mechanism is unclear.The aim of this study was to explore the effect of red meat on the occurrence and proliferation of colorectal cancer,and to further analyze the mechanism of action using a mouse model with primary colorectal cancer tumors.The results showed that the intervention of heme iron can significantly increase the occurrence and development of colorectal cancer tumors.Western blot analysis further revealed that in the colon tissue of the animal model,heme iron stimulating colorectal cancer tumor mice,xanthine oxidase(XOD),p-H2 AX,and p-STAT3 expression levels were up-regulated,and the tumor tissue expression was more obvious than the adjacent tissues.Moreover,a certain dose of iron sucrose and LPS can up-regulate the expression of xanthine oxidase in macrophages differentiated into THP-1 induced by PMA.Through immunohistochemical experiments,the expression position of xanthine oxidase and the expression position of macrophages were overlapped in the mouse colon.The conclusion shows that heme iron can increase the tumorigenesis and development of colorectal tumor mice,and this phenomenon is related to the up-regulation of XOD expression.

关 键 词：红肉 血红素铁 结直肠癌 氧化应激 黄嘌呤氧化酶 

分 类 号：R735.34[医药卫生—肿瘤] TS201[医药卫生—临床医学]