中国肿瘤生物治疗杂志2026，Vol.33Issue(2)：181-189,9.DOI:10.3872/j.issn.1007-385x.2026.02.010
结肠上皮细胞NCM460中线粒体DNA部分缺失诱导其恶性转化及免疫逃逸
Mitochondrial DNA(mtDNA)partial depletion induces malignant transformation and immune escape in colonic epithelial cell NCM460
摘要
Abstract
Objective:To clarify the effects of mitochondrial DNA(mtDNA)partial depletion on colonic epithelial cell NCM460.Methods:Mitochondrial DNA partially depleted cell model(mtDNA-reduced)and reversion model(reverted)were established by ethidium bromide(EB)induction.Mitochondrial function was evaluated by CCK-8(Cell Counting Kit-8)assay,reactive oxygen species(ROS)and mitochondrial membrane potential(JC-1)detection.Metabolic phenotypes were assessed by glucose,lactate and glycolytic key enzyme activity assays.Cell invasion and epithelial-mesenchymal transition(EMT)were detected by Transwell invasion assay and Western blot.Anoikis resistance was examined by polyHEMA coated culture.The PI3K/Akt/mTOR signaling pathway and programmed death ligand 1(PD-L1)expression were detected,and verified by PI3K inhibitor LY294002.Results:GEPIA(Gene Expression Profiling Interactive Analysis)database analysis showed that mtDNA-encoded genes were down-regulated in colorectal cancer(P＜0.05).Tissue microarray showed that cytochrome coxidase subunit 1(COX1)protein was highly expressed in normal colonic tissues but lowly expressed in cancer tissues(P＜0.05).Mitochondrial DNA-reduced NCM460 cells showed impaired mitochondrial function(decreased growth rate,reduced ROS generation,and decreased mitochondrial membrane potential,P＜0.05),exhibited the Warburg effect(increased glucose uptake,enhanced lactate secretion,and increased glycolytic key enzyme activity,P＜0.05),enhanced invasion capacity(P＜0.05)with EMT,and resisted anoikis(P＜0.05).The PI3K/Akt/mTOR pathway was activated and PD-L1 expression was upregulated in these cells.After treatment with LY294002,the glucose content showed a decreasing trend(P＞0.05),the cell activity decreased(P＜0.05),and PD-L1 expression was downregulated(P＜0.05).Conclusion:Partial depletion of mtDNA in colonic epithelial cell NCM460 can induce malignant transformation and immune escape.关键词
线粒体DNA/NCM460细胞/恶性转化/免疫逃逸/Warburg效应/程序性死亡配体1Key words
mitochondrial DNA(mtDNA)/NCM460/malignant transformation/immune escape/Warburg effect/programmed death ligand 1(PD-L1)分类
医药卫生引用本文复制引用
杨东梅,牟晶晶..结肠上皮细胞NCM460中线粒体DNA部分缺失诱导其恶性转化及免疫逃逸[J].中国肿瘤生物治疗杂志,2026,33(2):181-189,9.基金项目
湖北省自然科学基金青年项目(2021CFB267 （）
2021CFB294) （）
