[1]朱成军,魏世亮,赵娟,等.2-脱氧-D-葡萄糖通过PI3K/AKT通路调控线粒体自噬抑制非小细胞肺癌的机制研究[J].陕西医学杂志,2026,(9):1197-1201.[doi:DOI:10.3969/j.issn.1000-7377.2026.09.006]
　ZHU Chengjun,WEI Shiliang,ZHAO Juan,et al.Mechanism of 2-deoxy-D-glucose regulating PI3K/AKT pathway-mediated mitophagy in non-small cell lung cancer[J].,2026,(9):1197-1201.[doi:DOI:10.3969/j.issn.1000-7377.2026.09.006]
点击复制

2-脱氧-D-葡萄糖通过PI3K/AKT通路调控线粒体自噬抑制非小细胞肺癌的机制研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年9期
页码:
1197-1201
栏目:
基础研究
出版日期:
2026-09-05

文章信息/Info

Title:
Mechanism of 2-deoxy-D-glucose regulating PI3K/AKT pathway-mediated mitophagy in non-small cell lung cancer
作者:
朱成军; 魏世亮; 赵娟; 李瑞娜; 白海霞
（国药同煤总医院呼吸与危重症医学科，山西 大同 037054）
Author(s):
ZHU Chengjun; WEI Shiliang; ZHAO Juan; LI Ruina; BAI Haixia
(Department of Respiratory and Critical Care Medicine,China National Medicines Tongmei General Hospital,Datong 037054，China)
关键词:
2-脱氧-D-葡萄糖; 非小细胞肺癌; 磷脂酰肌醇-3激酶/蛋白激酶B信号通路; 线粒体; 自噬; 凋亡
Keywords:
2-DG; NSCLC; PI3K/AKT signaling pathway; Mitochondria; Autophagy; Apoptosis
分类号:
R 734.1
DOI:
DOI:10.3969/j.issn.1000-7377.2026.09.006
文献标志码:
A
摘要:
目的：探讨2-脱氧-D-葡萄糖（2-DG）通过调控磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）信号通路介导线粒体自噬，对非小细胞肺癌（NSCLC）A549细胞增殖、凋亡及线粒体功能的影响及其分子机制。方法：NSCLC A549细胞，随机分为五组：空白对照组、2-DG低剂量组（5 mmol/L）、2-DG中剂量组（10 mmol/L）、2-DG高剂量组（20 mmol/L）和LY294002组（20 μmol/LPI3K特异性抑制剂）。以CCK-8法检测细胞活力。流式细胞术测细胞凋亡率和线粒体活性氧（ROS）水平。以激光共聚焦显微镜测线粒体膜电位。以Western blot法检测PI3K/AKT通路及自噬相关蛋白表达。结果：与空白对照组比较，2-DG各剂量组及LY294002组细胞活力、侵袭能力降低，细胞凋亡率升高，呈剂量依赖性（均P<0.05），2-DG高剂量组以上指标与LY294002组相近（P＞0.05）。与空白对照组比较，2-DG低、中、高剂量组及LY294002组线粒体膜电位相对荧光强度降低，线粒体ROS相对荧光强度升高，且呈剂量依赖性（均P<0.05），2-DG高剂量组线粒体膜电位、ROS水平与LY294002组相近（均P＞0.05）。与空白对照组比较，2-DG低、中、高剂量组及LY294002组p-PI3K、p-AKT及p62蛋白相对表达降低，轻链3-Ⅱ（LC3Ⅱ）、轻链3-Ⅰ（LC3Ⅰ）蛋白表达升高，且均呈剂量依赖性（均P<0.05），2-DG高剂量组上述蛋白表达变化与LY294002组相近（均P>0.05）。结论：2-DG可通过抑制PI3K/AKT信号通路激活线粒体自噬，降低A549细胞活力并诱导其凋亡。
Abstract:
Objective:To investigate the effect of 2-deoxy-D-glucose (2-DG) on non-small cell lung cancer (NSCLC) A549 cells and mitochondrial function by regulating mitophagy through the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway.Methods:NSCLC A549 cells were selected and randomly divided into 5 groups:The control group,2-DG low dose group (5 mmol/L),2-DG middle dose group (10 mmol/L),2-DG high dose group (20 mmol/L) and LY294002 group (20 μmol/L) were treated with blank control,2-DG low dose group (5 mmol/L),2-DG middle dose group (10 mmol/L) and LY294002 group (20 μmol/L).Cell viability was detected by CCK-8 assay.Flow cytometry was used to detect the apoptosis rate and mitochondrial reactive oxygen species (ROS) level.Mitochondrial membrane potential was measured by laser confocal microscopy.Western blot was used to detect the expression of PI3K/AKT pathway and autophagy-related proteins.Results:Compared with the blank control group,cell viability and invasion ability were decreased,and the apoptosis rate was increased in the 2-DG dose groups and the LY294002 group in a dose-dependent manner (all P<0.05).The above indicators in the 2-DG high-dose group were similar to those in the LY294002 group (P>0.05).Compared with the blank control group,the relative fluorescence intensity of mitochondrial membrane potential was decreased,and the relative fluorescence intensity of mitochondrial reactive oxygen species (ROS) was increased in the 2-DG low-,medium-,and high-dose groups as well as the LY294002 group,all in a dose-dependent manner (all P<0.05).The mitochondrial membrane potential and ROS levels in the 2-DG high-dose group were similar to those in the LY294002 group (all P>0.05).Compared with the blank control group,the relative expression levels of p-PI3K,p-AKT,and p62 proteins were decreased,while the expression levels of LC3Ⅱ and LC3Ⅰ proteins were increased in the 2-DG low-,medium-,and high-dose groups and the LY294002 group,all in a dose-dependent manner (all P<0.05).The changes in the expression of the above proteins in the 2-DG high-dose group were similar to those in the LY294002 group (all P>0.05).Conclusion:2-DG can activate mitophagy by inhibiting the PI3K/AKT signaling pathway,thereby reducing A549 cell viability and inducing apoptosis.

参考文献/References:

[1]TEPPALA S,KOO J,CLARKE S,et al.Cost-effectiveness of pembrolizumab plus chemotherapy for metastatic non-small cell lung cancer:A head-to-head trial vs.real-world comparison[J].J Med Econ,2026,29(1):1099-1110.
[2]何婷,李雨玲,熊军芳.慢性阻塞性肺疾病合并非小细胞肺癌患者血清miR-145-5p、miR-150-5p表达与病理特点和预后的关系研究[J].空军军医大学学报,2025,46(10):1340-1345.
[3]柴丽敏,郝志英.EGFR抑制剂联合放疗治疗晚期非小细胞肺癌的临床效果及其皮疹发生与生存时间的关系[J].临床误诊误治,2020,33(9):43-47.
[4]胡海峰,雒小佳.2-脱氧葡萄糖联合奥希替尼对非小细胞肺癌细胞株H1975耐药性、糖酵解水平表达和增殖活性的影响[J].检验医学与临床,2022,19(19):2620-2622,2627.
[5]孙露露,吴晓,季娟娟,等.基于PI3K/AKT信号通路探讨白芍总苷胶囊对非小细胞肺癌增殖、迁移、侵袭和凋亡的影响[J].海南医科大学学报,2025,31(12):900-908.
[6]李之坚,张冰,刘宁.细胞分裂周期蛋白20通过激活PI3K/Akt/mTOR通路驱动非小细胞肺癌吉非替尼耐药[J].中国生物化学与分子生物学报,2025,41(8):1159-1168.
[7]RAJENDIRAN S,PRASATH S,RAMESH N,et al.Hispidulin-mediated inhibition of lung cancer progression through PI3K/AKT Signaling:A combined bioinformatic analysis and experimental investigation[J].Cytotechnology,2026,78(3):82.
[8]EL-FATTAH W A,GUESMI A,BEN HAMADI N,et al.Development of a multi-targeted sulfonyl-bridged bisselenadiazole derivative as a potent EGFR/PI3K/AKT/mTOR modulator in lung adenocarcinoma[J].RSC Adv,2026,16(22):19903-19919.
[9]杨兵,胡文文,孙仲涛,等.肺叶切除术和亚肺叶切除术治疗早期非小细胞肺癌的临床效果及对短期预后的影响[J].临床误诊误治,2020,33(9):97-101.
[10]LIU H,WANG M,PANG Y.RHCG inhibition promotes the sensitivity of PIK3CA-mutant non-small lung cancer to PI3K inhibitor[J].Histol Histopathol,2026,41(4):629-639.
[11]焦健方,张佳.早期非小细胞肺癌经PD-1抑制剂与立体定向体部放疗联合治疗的疗效观察研究[J].陕西医学杂志,2026,55(1):48-52.
[12]钱薇,顾天,褚明亮,等.紫草素通过糖酵解代谢途径对肺癌A549细胞增殖、迁移和侵袭的抑制作用[J].中成药,2024,46(11):3814-3818.
[13]胡先华,赵春艳,张海迪,等.2-脱氧-D-葡萄糖通过诱导人非小细胞肺癌细胞线粒体功能障碍抑制肿瘤细胞增殖[J].中国免疫学杂志,2021,37(7):829-833.
[14]郝帅,卢从华,林采余,等.2-脱氧葡萄糖逆转非小细胞肺癌细胞对奥希替尼继发性耐药的作用及机制[J].中华结核和呼吸杂志,2019,42(3):198-205.
[15]吴高平,孟杭锋,陈燕敏,等.青蒿琥酯及其联合2-脱氧-D-葡萄糖对非小细胞肺癌A549细胞的抑制作用[J].江苏医药,2022,48(11):1085-1089,封2.
[16]闫雨廷,周妍,吴巍.萝卜硫素调控自噬相关蛋白抑制非小细胞肺癌线粒体自噬[J].山西医科大学学报,2020,51(1):1-6.
[17]张天意,杨鹏飞,王菊芳,等.碳离子诱发线粒体损伤抑制非小细胞肺癌细胞增殖机理[J].辐射研究与辐射工艺学报,2024,42(4):64-74.
[18]张磊,赵永强,刘公哲,等.非小细胞肺癌患者组织中自噬相关蛋白Beclin1、LC3、p62的表达水平及临床意义[J].临床和实验医学杂志,2023,22(19):2054-2057.
[19]姜承奇,崔雪萍,郑莉,等.自噬与铁死亡在肺癌发生发展及治疗中的研究进展[J].中国肺癌杂志,2025,28(10):777-786.
[20]CHAN A A,SANKAR K,RECKAMP K L,et al.Elevated co-expression of TIMM17A and NMT1 is associated with poor survival in non-small cell lung cancer[J].Sci Rep,2025,15(1):35597.
[21]CHEN K,GAO X,LI J,et al.New activities of homoyessotoxin against lung cancer through the regulation of EGFR/PI3K/AKT pathway[J].Mar Life Sci Technol,2026,8(1):144-163.
[22]ZHUANG X,LIN S,ZHANG C S,et al.APMAP regulated by YY1 transcription mediates ferroptosis and metastasis in non-small cell lung cancer through the PI3K/AKT/mTOR pathway[J].J Mol Histol,2026,57(1):27.
[23]HUANG T,ZHANG C,SHANG Z,et al.Bone mesenchymal stem cells improve cholestatic liver fibrosis by targeting ULK1 to regulate autophagy through PI3K/AKT/mTOR pathway[J].Stem Cells Transl Med,2024,13(7):648-660.
[24]WANG X,ZHANG Y,LI H,et al.Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease[J].Zhongguo Zhen Jiu,2025,45(10):1450-1458.
[25]赵智,董仁松.铜绿假单胞菌注射液对肺癌A549细胞自噬及PI3K/Akt通路的影响[J].临床肺科杂志,2021,26(2):260-265.

相似文献/References:

[1]王晓东,景鹏宇△,崔 凯,等.术前外周血中性粒细胞淋巴细胞比值对ⅠⅢ期非小细胞肺癌患者预后的影响[J].陕西医学杂志,2019,(12):1612.
[2]彭 峰,彭奕华,张宏华,等.非小细胞肺癌化疗前后血清糖类抗原125、肿瘤异常蛋白水平变化及其与疗效的关系[J].陕西医学杂志,2020,49(7):851.[doi:DOI:10.3969/j.issn.10007377.2020.07.023]
　PENG Feng,PENG Yihua,ZHANG Honghua,et al.Changes of serum CA125 and TAP levels before and after chemotherapy for non-small cell lung cancer and their relationship with curative effect[J].,2020,49(9):851.[doi:DOI:10.3969/j.issn.10007377.2020.07.023]
[3]杨 昕,刘 芳,杜 静,等.肺癌癌组织中过氧化物酶增殖体激活受体γ基因表达水平对培美曲塞化疗疗效的预测价值*[J].陕西医学杂志,2020,49(10):1359.[doi:DOI:10.3969/j.issn.1000-7377.2020.10.042]
　YANG Xin,LIU Fang,DU Jing,et al.Predictive value of PPARγ gene expression level in lung cancer tissue for curative effect of pemetrexed chemotherapy[J].,2020,49(9):1359.[doi:DOI:10.3969/j.issn.1000-7377.2020.10.042]
[4]王晓东,吕 峰△,崔 凯.ⅢA-N2期非小细胞肺癌纵隔淋巴结跳跃性转移临床特点及对预后的影响[J].陕西医学杂志,2020,49(12):1634.[doi:DOI:10.3969/j.issn.1000-7377.2020.12.025]
[5]苏艳丽,李 波.Th9细胞对非小细胞肺癌患者CD8+T细胞抗肿瘤活性的调控作用[J].陕西医学杂志,2021,50(1):15.[doi:DOI:10.3969/j.issn.1000-7377.2021.01.004]
　SU Yanli,LI Bo.Regulatory of Th9 cells on anti-tumor activity of CD8+T cells in patients with non-small-cell lung cancer[J].,2021,50(9):15.[doi:DOI:10.3969/j.issn.1000-7377.2021.01.004]
[6]岳 英,董锦华,肖月梅.肺免疫微环境中调节因子表达对肿瘤生长和转移的影响[J].陕西医学杂志,2021,50(4):495.[doi:DOI:10.3969/j.issn.1000-7377.2021.04.030]
[7]崔 凯,白峻峰,支亚男,等.外泌体微小RNA-23a对非小细胞肺癌血管生成的影响及机制研究[J].陕西医学杂志,2021,50(9):1048.[doi:DOI:10.3969/j.issn.1000-7377.2021.09.002]
　CUI Kai,BAI Junfeng,ZHI Ya'nan,et al.Effect of exosome miR-23a on angiogenesis in NSCLC and its mechanism[J].,2021,50(9):1048.[doi:DOI:10.3969/j.issn.1000-7377.2021.09.002]
[8]陈 彦,姜立朋.基于CT的影像组学特征对非小细胞肺癌放射治疗效果的评估价值[J].陕西医学杂志,2021,50(9):1094.[doi:DOI:10.3969/j.issn.1000-7377.2021.09.013]
　CHEN Yan,JIANG Lipeng.Evaluation value of CT-based imaging omics features for radiotherapy effect in treatment of non-small cell lung cancer[J].,2021,50(9):1094.[doi:DOI:10.3969/j.issn.1000-7377.2021.09.013]
[9]崔 凯,支亚男,王壮壮,等.微小RNA-30对非小细胞肺癌侵袭、转移能力的影响及机制研究[J].陕西医学杂志,2021,50(10):1214.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.009]
　CUI Kai,ZHI Ya'nan,WANG Zhuangzhuang,et al.Effect and mechanism of miR-30 on invasion and metastasis of non-small cell lung cancer[J].,2021,50(9):1214.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.009]
[10]梁乐乐,王 鹏,刘俊霞,等.非小细胞肺癌组织中T细胞免疫球蛋白区黏蛋白-3、程序性死亡因子-1及程序性因子配体1的表达分析[J].陕西医学杂志,2021,50(10):1227.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.012]
　LIANG Lele,WANG Peng,LIU Junxia,et al.Expression of TIM-3,PD-1 and PD-L1 in non-small cell lung cancer[J].,2021,50(9):1227.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.012]

备注/Memo

备注/Memo:
山西省自然科学基金资助项目（2024SRZ-10263）
更新日期/Last Update: 2026-09-15