[1]康思阳,马文星,黄杏,等.RasGTPase激活蛋白结合蛋白1通过促进应激颗粒形成增强非小细胞肺癌顺铂耐药性的作用及机制[J].陕西医学杂志,2026,(4):446-455.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.003]
　KANG Siyang,MA Wenxing,HUANG Xing,et al.The role and mechanism of G3BP1 in enhancing cisplatin resistance in nonsmall cell lung cancer through the promotion of stress granule formation[J].,2026,(4):446-455.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.003]
点击复制

RasGTPase激活蛋白结合蛋白1通过促进应激颗粒形成增强非小细胞肺癌顺铂耐药性的作用及机制

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

卷:
期数:
2026年4期
页码:
446-455
栏目:
基础研究
出版日期:
2026-04-05

文章信息/Info

Title:
The role and mechanism of G3BP1 in enhancing cisplatin resistance in nonsmall cell lung cancer through the promotion of stress granule formation
作者:
康思阳1; 马文星2; 黄杏2; 徐卉2; 贾小芬2; 谭延振2; 郭凯2; 温红侠1; 3
（1.陕西中医药大学临床医学院，陕西 咸阳 712046；2.陕西省人民医院胸外科,陕西 西安 710068；3.陕西省人民医院呼吸内二科,陕西 西安 710068）
Author(s):
KANG Siyang1; MA Wenxing2; HUANG Xing2; XU Hui2; JIA Xiaofen2; TAN Yanzhen2; GUO Kai2; WEN Hongxia1; 3 
（1.Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang 712046,China；2.Department of Thoracic Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;3.Departmentof Respiratory Medicine Ⅱ,Shaanxi Provincial People’s Hospital,Xi’an 710068,China）
关键词:
非小细胞肺癌; Ras-GTPase激活蛋白结合蛋白1; 顺铂耐药性; 氧化应激; 应激颗粒; 预后
Keywords:
Nonsmall cell lung cancer; Ras-GTPaseactivating proteinbinding protein 1; Chemotherapy resistance; Oxidative stress;  Stress granules; Prognosis
分类号:
R 734.2
DOI:
DOI:10.3969/j.issn.1000-7377.2026.04.003
文献标志码:
A
摘要:
目的：探讨Ras-GTPase激活蛋白结合蛋白1（G3BP1）在非小细胞肺癌（NSCLC）顺铂（CD-DP）化疗耐药中的作用及相关分子机制。方法：利用TCGA和GTEx数据库分析G3BP1在NSCLC组织中的表达及与患者预后的关系。在体外实验中，采用免疫荧光法（IF）观察CD-DP诱导的应激颗粒（SGs）的形成，以DCFH-DA探针检测细胞内活性氧（ROS）的水平；构建G3BP1过表达与敲减的A549细胞系，采用CCK-8法检测细胞对CD-DP的敏感性（IC50值），流式细胞术（FCM）分析细胞凋亡，并探讨G3BP1对ROS水平及SGs形成的影响。在体内实验中，建立裸鼠皮下移植瘤模型，验证G3BP1对肿瘤生长及CD-DP疗效的调控作用。结果：①数据库分析显示，G3BP1在NSCLC组织中显著高表达，且高表达患者总生存期较短（P<0.05）。②体外实验表明，敲减G3BP1可显著增强A549细胞对CD-DP的敏感性，促进凋亡，并导致细胞内ROS积聚及SGs形成减少；过表达G3BP1则产生相反效果，即细胞CD-DP IC50升高、凋亡减少，并伴随ROS水平下降和SGs形成增加（均P<0.05）。③体内实验进一步证实，G3BP1过表达促进移植瘤生长并诱导CD-DP耐药，敲减G3BP1则抑制肿瘤生长并增强CD-DP的治疗效果（均P<0.05）。结论：G3BP1通过促进SGs形成、缓解CD-DP引发的氧化应激，从而增强NSCLC的CD-DP耐药性。G3BP1是NSCLC化疗耐药的关键调控因子，有望成为潜在的预后生物标志物和逆转耐药的治疗靶点。
Abstract:
Objective:To investigate the role and underlying mechanism of Ras-GTPaseactivating proteinbinding protein 1 （G3BP1） in the chemoresistance of nonsmall cell lung cancer （NSCLC）.Methods：The expression of G3BP1 in NSCLC tissues and its correlation with patient prognosis were analyzed using data from The Cancer Genome Atlas （TCGA） and the GenotypeTissue Expression （GTEx） databases.In vitro,the formation of cisplatininduced stress granules （SGs） was observed by immunofluorescence staining,and intracellular reactive oxygen species （ROS） levels were measured using the DCFH-DA probe.A549 cell lines with G3BP1 overexpression and knockdown were established,and cisplatin sensitivity （IC50） was assessed using the Cell Counting Kit8 （CCK-8） assay.Flow cytometry was used to analyze cell apoptosis,and the impact of G3BP1 on ROS levels and SGs formation was further explored.In vivo,a subcutaneous xenograft model in nude mice was established to validate the regulatory effects of G3BP1 on tumor growth and the efficacy of cisplatin treatment.Results:Database analysis revealed that G3BP1 is significantly upregulated in NSCLC tissues,and high expression of G3BP1 is associated with shorter overall survival in patients （P<0.05）.In vitro experiments demonstrated that knockdown of G3BP1 significantly enhanced the sensitivity of A549 cells to cisplatin,promoted apoptosis,and resulted in reduced accumulation of intracellular ROS and decreased formation of SGs.Conversely,overexpression of G3BP1 had the opposite effect,leading to an increased cisplatin IC50,reduced apoptosis,and a decrease in ROS levels alongside an increase in SGs formation （all P<0.05）.In vivo experiments further confirmed that G3BP1 overexpression promoted tumor growth and induced cisplatin resistance,while G3BP1 knockdown inhibited tumor growth and enhanced the therapeutic efficacy of cisplatin （all P<005）.Conclusion:G3BP1 enhances cisplatin resistance in NSCLC by promoting stress granule formation and mitigating cisplatininduced oxidative stress.G3BP1 is a key regulatory factor in chemoresistance in NSCLC and holds potential as a prognostic biomarker and a therapeutic target for overcoming drug resistance.

参考文献/References:

[1]SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71（3）：209-249.
[2]LI Z,HU Y,XU C,et al.Prognostic significance of methyl-cpG binding domain4 polymorphism rs140693 and clinical characteristics in chinese lung cancer patients[J].Phenomics,2024,4（5）：453-464.
[3]WU F,WANG H,TAO H,et al.Comparison of value of biomarkers in diagnosing lung cancer：An overview of systematic reviews protocol[J].Medicine （Baltimore）,2019,98（19）：e15525.
[4]赵钰玲,董娅,范亚莉,等.吉西他滨对人非小细胞肺癌A549、H1299细胞增殖及凋亡的影响[J].陕西医学杂志,2017,46（6）：683-685，708.
[5]CHEN Y X,WANG C J,XIAO D S,et al.eIF3a R803K mutation mediates chemotherapy resistance by inducing cellular senescence in small cell lung cancer[J].Pharmacol Res,2021,174：105934.
[6]CAMPELO M M,REIS-DAS-MERCêS L,VIDAL A F,et al.The dual role of circHIPK3 in cancer and its implications for multiple drugs resistance：A systematic review and computational approach[J].Front Oncol,2025,15：1547889.
[7]HERZOG B H,DEVARAKONDA S,GOVINDAN R.Overcoming chemotherapy resistance in SCLC[J].J Thorac Oncol,2021,16（12）：2002-2015.
[8]QIAN M,WAN Z,LIANG X,et al.Targeting autophagy in HCC treatment：Exploiting the CD147 internalization pathway[J].Cell Commun Signal,2024,22（1）：583.
[9]ZHAO J,FU X,CHEN H,et al.G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer[J].Br J Cancer,2021,124（2）：425-436.
[10]LIU C,ZHOU L,CHEN J,et al.Galectin-7 promotes cisplatin efficacy by facilitating apoptosis and G3BP1 degradation in cervical cancer[J].Biochem Pharmacol,2023,217：115834.
[11]LI Q J,FANG X L,LI Y Q,et al.DCAF7 acts as a scaffold to recruit USP10 for G3BP1 deubiquitylation and facilitates chemoresistance and metastasis in nasopharyngeal carcinoma[J].Adv Sci （Weinh）,2024,11（36）：e2403262.
[12]WANG Z,CHANG X,ZHU G,et al.Depletion of lncRNA MALAT1 inhibited sunitinib resistance through regulating miR-362-3p-mediated G3BP1 in renal cell carcinoma[J].Cell Cycle,2020,19（16）：2054-2062.
[13]GE Y,JIN J,LI J,et al.The roles of G3BP1 in human diseases （review）[J].Gene,2022,821：146294.
[14]ZHANG Z,ZHANG C,YANG Z,et al.m（6）A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer[J].J Hematol Oncol,2021,14（1）：190.
[15]苏晓兰,刘晓梅.非小细胞肺癌组织中趋化因子受体、硫酸软骨素蛋白的表达及其临床意义[J].陕西医学杂志,2025,54（10）：1420-1423，1431.
[16]HENDRIKS L E L,REMON J,FAIVRE-FINN C,et al.Non-small-cell lung cancer[J].Nat Rev Dis Primers,2024,10（1）：71.
[17]冯谢敏,赵红,崔洁,等.同步放化疗治疗局部晚期非小细胞肺癌疗效观察[J].陕西医学杂志,2016,45（9）：1126-1128.
[18]郭亚焕.康艾注射液联合化疗治疗晚期非小细胞肺癌疗效观察[J].陕西中医,2015,36（10）：1322-1323.
[19]张永庆,尚立群,苗毅,等.多西他赛联合顺铂治疗晚期非小细胞肺癌疗效观察[J].陕西医学杂志,2015,44（8）：1074-1075.
[20]曾瑞,钟红卫.益气养阴法治疗中晚期非小细胞肺癌的临床疗效观察[J].陕西中医,2016,37（2）：164-165.
[21]MIN H Y,LEE H Y.Mechanisms of resistance to chemotherapy in non-small cell lung cancer[J].Arch Pharm Res,2021,44（2）：146-164.
[22]BI Y Y,CHEN Q,YANG M Y,et al.Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer[J].Nat Commun,2024,15（1）：2759.
[23]CHEN R,WANG J,HUANG S,et al.Carnitine palmitoyltransferase 1C promotes EMT-associated cisplatin resistance in non-small cell lung cancer cells[J].Cancer Biol Med,2025,22（1）：48-66.
[24]XU Y,MENG Y,XU Y,et al.Epigenetic mechanisms in non-small cell lung cancer therapy and chemoresistance[J].Biochim Biophys Acta Rev Cancer,2025,1880（4）：189356.
[25]ZHOU K,LI S,ZHAO Y,et al.Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer[J].Front Immunol,2023,14：1127071.
[26]曹勇熬,马民,陈孝银,等.补肾化瘀解毒方荷瘤药物血清对A549/DDP耐药逆转作用的研究[J].陕西中医,2004,25（7）：663-665.
[27]LI Y,WANG J,ZHONG S,et al.Overexpression of G3BP1 facilitates the progression of colon cancer by activating β-catenin signaling[J].Mol Med Rep,2020,22（5）：4403-4411.
[28]FREIBAUM B D,MESSING J,NAKAMURA H,et al.Identification of small molecule inhibitors of G3BP-driven stress granule formation[J].Bio Rxiv,2023，223（3）：e202308083.
[29]SONG M S,GRABOCKA E.Stress granules in cancer[J].Rev Physiol Biochem Pharmacol,2023,185：25-52.
[30]YUAN L,MAO L H,HUANG Y Y,et al.Stress granules：Emerging players in neurodegenerative diseases[J].Transl Neurodegener,2025,14（1）：22.
[31]FANG M,LUO L,CHEN Y,et al.Perillaldehyde improves parkinson-like deficits by targeting G3BP mediated stress granule assembly in preclinical models[J].Adv Sci （Weinh）,2025,12（14）：e2412152.
[32]ZHONG Z,YANG S,LIU D,et al.Stress granule dynamics govern TOR reactivation and growth recovery during post-heat stress adaptation[J].Sci Adv,2025,11（51）：eadv6202.
[33]CHEN H Y,LIN L T,WANG M L,et al.Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma[J].Biochim Biophys Acta Mol Basis Dis,2018,1864（5 Pt A）：1850-1861.
[34]MACAULEY R C.The limits of “life-limiting”[J].J Pain Symptom Manage,2019,57（6）：1176-1181.
[35]HSU L,NDAO A.Diffraction-limited broadband optical meta-power-limiter[J].Opt Lett,2021,46（6）：1293-1296.

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(4):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(4):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(4):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(4):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(4):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(4):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(4):1227.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.012]

备注/Memo

备注/Memo:
国家自然科学基金资助项目（82203758）；陕西省自然科学基金资助项目（2025JCYBMS919）
更新日期/Last Update: 2026-04-05