广东药科大学学报2026，Vol.42Issue(2)：88-100,13.DOI:10.16809/j.cnki.2096-3653.2025121203
基于c-Myc/HIF1α/多胺途径探讨结直肠癌进程中肠黏膜屏障功能紊乱的发生机制
Mechanistic insights into intestinal mucosal barrier dysfunction in colorectal cancer based on the c-Myc/HIF1α/polyamine axis
摘要
Abstract
Objective To explore the molecular mechanism by which human colon cancer cell line HCT116 deprives normal intestinal mucosal tissue of polyamines to meet its energy needs through activating the c-Myc/HIF1α pathway,ultimately leading to intestinal epithelial barrier dysfunction in colon cancer.Methods HCT116 cells with different levels of HIF1α expression were co-cultured with IEC6 cells for 24,48,72,and 96 hours.The intestinal mucosal barrier function was assessed by measuring transepithelial electrical resistance(TEER),FD4 permeability,and tight junction proteins(ZO-1,Occludin).Intracellular polyamine content was detected using HPLC.The effect of exogenous spermidine on HCT116 proliferation was analyzed using the CCK8 method.Interventions with DFMO,2DG,and c-Myc inhibitors were conducted to examine glycolysis indicators(glucose consumption,lactate production,lactate dehydrogenase(LDH)activity,ATP levels)and the expression of key proteins(HK2,GLUT1,LDHA,PKM2,HIF1α,c-Myc,ODC,SLC22A1),aiming to elucidate the molecular mechanism.Results Upregulation of HIF1α exacerbated the polyamine deprivation of HCT116 cells from IEC6,leading to impaired intestinal barrier function(decreased TEER,increased FD4,and downregulation of ZO-1/Occludin).Exogenous spermidine promoted HCT116 proliferation and glycolysis through the c-Myc/HIF1α pathway.Hypoxia-induced HIF1α inhibited ODC expression and reduced polyamine synthesis within the tumor,forcing HCT116 to deprive IEC6 of polyamines to maintain energy metabolism.Conclusion The c-Myc/HIF1α signaling axis in HCT116 cells drives tumor glycolysis,disrupts the intestinal mucosal barrier,and promotes colorectal cancer progression by depriving the gut of polyamines.This discovery provides a new strategy for targeting the polyamine metabolism pathway to prevent and treat colorectal cancer.关键词
结直肠癌/多胺/糖酵解/肠道屏障损伤Key words
colorectal cancer/polyamine/glycolysis/intestinal barrier damage分类
医药卫生引用本文复制引用
帅雅静,林思琪,靳淑颖,王桂香..基于c-Myc/HIF1α/多胺途径探讨结直肠癌进程中肠黏膜屏障功能紊乱的发生机制[J].广东药科大学学报,2026,42(2):88-100,13.基金项目
国家自然科学基金项目(81873225) （81873225）
