中国肿瘤生物治疗杂志2025，Vol.32Issue(8)：799-805,7.DOI:10.3872/j.issn.1007-385x.2025.08.002
甲硫氨酸限制对肺腺癌细胞增殖及磷酸戊糖途径的影响
Effects of methionine restriction on the proliferation and the pentose phosphate pathway of lung adenocarcinoma cells
摘要
Abstract
Objective:To investigate the impact of methionine restriction on the proliferation and apoptosis of lung adenocarcinoma(LUAD)cells,and the pentose phosphate pathway.Methods:LUAD cells H1299 and A549 were assigned to the Met+(100 μmol/L methionine)and Met-(0 μmol/L methionine)groups and cultured continuously for 4 d.Cell counting was used to evaluate the effects of methionine treatment on the proliferation of H1299 and A549 cells.Cell-cycle distribution was detected by PI staining;Cell apoptosis by Annexin Ⅴ-PE/7AAD labeling;intracellular ROS level by DCFH-DA probe;intracellular NADPH and GSH levels by WST-8 and DTNB assays,respectively.The Cancer Genome Atlas(TCGA)was used to analyze the correlations between the expressions of glucose-6-phosphate dehydrogenase(G6PD)and 6-phosphogluconate dehydrogenase(6PGD)and the methionine-metabolic pathway.WB assay was employed to evaluate the effects of methionine restriction and supplementation of S-adenosylmethionine(SAM),a downstream methionine metabolic product,on the expressions of G6PD and 6PGD,key enzymes in the pentose phosphate pathway,in LUAD cells.Results:Methionine restriction significantly inhibited the proliferation of H1299 and A549 cells(both P<0.01),arrested cells in G2/M phase(both P<0.05),elevated total ROS levels(both P<0.001),and induced apoptosis(both P<0.001).Furthermore,methionine restriction significantly reduced NADPH and GSH levels(both P<0.01)and suppressed DNA synthesis(both P<0.01).TCGA analysis revealed positive correlations between G6PD/6PGD expression levels and the methionine metabolic pathway(both P<0.001).Methionine restriction down-regulated the expressions of G6PD and 6PGD proteins(both P<0.01),whereas SAM supplementation partially restored their expressions(both P<0.01),suggesting that methionine regulated the pentose phosphate pathway through SAM.Conclusion:Methionine restriction suppresses LUAD cell proliferation by inhibiting the PPP,which provides experimental evidence for methionine-restriction therapy for LUAD.关键词
甲硫氨酸/肺腺癌/磷酸戊糖途径/氧化应激/增殖/凋亡Key words
methionine/lung adenocarcinoma(LUAD)/pentose phosphate pathway(PPP)/oxidative stress/proliferation/apoptosis分类
医药卫生引用本文复制引用
李玉玉,黎世日,李智莹,赵正刚,李芳红,赵子建,周素瑾..甲硫氨酸限制对肺腺癌细胞增殖及磷酸戊糖途径的影响[J].中国肿瘤生物治疗杂志,2025,32(8):799-805,7.基金项目
国家自然科学基金(No.82403321) （No.82403321）
广州市科技计划项目(No.2023B03J1291) （No.2023B03J1291）
广东省基础与应用基础研究(No.2023A1515110036) （No.2023A1515110036）
