今日药学

SOX-2过表达促进EGFR突变肺腺癌细胞对奥希替尼的耐药性：1项体外初步研究

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张宜之 , 王倍 , 王雅文 , 唐可京 ^*

今日药学 | 论著 2026,36(7): 505-511

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今日药学 |论著 2026 , 36 (7) : 505 -511

SOX-2过表达促进EGFR突变肺腺癌细胞对奥希替尼的耐药性：1项体外初步研究

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张宜之, 王倍, 王雅文, 唐可京^*

作者信息

中山大学附属第一医院药学部，广东　广州　510080

通讯作者:

唐可京，主任医师，研究方向：肺癌及其他呼吸性疾病，E-mail：tangkj@mail.sysu.edu.cn

作者简介:

张宜之，助理研究员，研究方向：肿瘤药理学

Overexpression of SOX-2 Promotes Osimertinib Resistance in EGFR-Mutated Lung Adenocarcinoma Cells: A Preliminary in vitro Study

Yizhi ZHANG, Bei WANG, Yawen WANG, Kejing TANG^*

Affiliations

The Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China

出版时间: 2026-07-25 doi: 10.12048/j.issn.1674-229X.2026.07.004

文章导航

摘要

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目的

EGFR突变肺腺癌患者对奥希替尼等靶向药物常出现获得性耐药，导致预后不良。肿瘤干细胞特性是耐药形成的重要机制，其中干性基因SOX-2在奥希替尼耐药中的作用尚未明确。本研究旨在探讨SOX-2在EGFR突变肺腺癌奥希替尼耐药中的功能。

方法

本研究首先利用GEPIA、TIMER和HPA公开数据库对SOX-2在肺腺癌中表达及其水平与预后的相关性进行分析。另外在肺腺癌细胞系H1975与PC9中过表达SOX-2，采用CCK-8法检测细胞对奥希替尼的敏感性，并通过3D-Matrigel培养实验评估细胞成球能力。

结果

SOX-2过表达显著增强了H1975和PC9细胞对奥希替尼的耐药性，并提升其三维培养条件下的克隆形成与生长能力。

结论

SOX-2高表达可促进EGFR突变肺腺癌对奥希替尼的耐药，本研究将为EGFR突变肺腺癌的预后评估提供实验依据。

关键词

干性基因 / SOX-2 / EGFR突变肺腺癌 / 奥希替尼耐药

Abstract

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OBJECTIVE

Patients with EGFR-mutated lung adenocarcinoma often develop acquired resistance to targeted drugs such as Osimertinib，leading to poor prognosis. Tumor stem cell properties are an important mechanism for drug resistance，and the role of the stemness gene SOX-2 in Osimertinib resistance remains unclear. This study aimed to investigate the function of SOX-2 in Osimertinib resistance in EGFR-mutated lung adenocarcinoma.

METHODS

This study first analyzed the expression of SOX-2 in lung adenocarcinoma and its correlation with prognosis using the public databases GEPIA，TIMER，and HPA. Additionally，SOX-2 was overexpressed in lung adenocarcinoma cell lines H1975 and PC9，and cellular sensitivity to Osimertinib was assessed using the CCK-8 assay. Sphere-forming capacity was evaluated via 3D Matrigel culture assay.

RESULTS

Overexpression of SOX-2 significantly enhanced the resistance of H1975 and PC9 cells to Osimertinib and enhanced their clonogenic capacity and proliferative ability under three-dimensional culture conditions.

CONCLUSION

High SOX-2 expression promotes Osimertinib resistance in EGFR-mutated lung adenocarcinoma，and this study provides experimental evidence for the prognosis assessment of EGFR-mutated lung adenocarcinoma.

Key words

stemness gene / SOX-2 / EGFR-mutated lung adenocarcinoma / Osimertinib resistance

引用本文

张宜之, 王倍, 王雅文, 唐可京. SOX-2过表达促进EGFR突变肺腺癌细胞对奥希替尼的耐药性：1项体外初步研究. 今日药学, 2026 , 36 (7) : 505 -511 . DOI: 10.12048/j.issn.1674-229X.2026.07.004

Yizhi ZHANG, Bei WANG, Yawen WANG, Kejing TANG. Overexpression of SOX-2 Promotes Osimertinib Resistance in EGFR-Mutated Lung Adenocarcinoma Cells: A Preliminary in vitro Study[J]. Pharmacy Today, 2026 , 36 (7) : 505 -511 . DOI: 10.12048/j.issn.1674-229X.2026.07.004

基金

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中国博士后科学基金(2025M773584)
广东省医院药学研究基金——肿瘤支持治疗研究基金（复星基金）立项项目(2024A02010)

参考文献

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参考文献引证文献

排序方式：

[1]

Xu J Y, Zhang C C, Wang X, et al. Integrative proteomic characterization of human lung adenocarcinoma[J]. Cell, 2020, 182(1): 245-261. e17.

[2]

王洁, 王志杰, 徐佳晨, 等. EGFR-TKIs耐药后应对策略及标准化质量控制中国专家共识[J]. 中国肿瘤临床与康复, 2025, 32(9): 547-572.

[3]

Fu K, Xie F C, Wang F, et al. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance[J]. J Hematol Oncol, 2022, 15(1): 173.

[4]

Zalaquett Z, Catherine R H M, Kassis Y, et al. Acquired resistance mechanisms to osimertinib: the constant battle[J]. Cancer Treat Rev, 2023, 116: 102557.

[5]

Roper N, Brown A L, Wei J S, et al. Clonal evolution and heterogeneity of osimertinib acquired resistance mechanisms in EGFR mutant lung cancer[J]. Cell Rep Med, 2020, 1(1): 100007.

[6]

Guo W J, Luan J Y, Miao Y X. Abstract 924: Tumor-initiating stem cells fine-tune the plasticity of neutrophils to sculpt a protective niche[J]. Cancer Res, 2025, 85(8): 924.

[7]

Tang Q, Chen J H, Di Z Y, et al. TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer[J]. J Exp Clin Cancer Res, 2020, 39(1): 232.

[8]

江懿. Mex3a调控靶基因Sox2介导膀胱癌淋巴结转移和肿瘤干性[D]. 南昌: 南昌大学, 2024.

[9]

孙红岗, 何丽钦, 夏颖. 肿瘤干细胞标志物SOX2在甲状腺癌中的临床应用价值[J]. 全科医学临床与教育, 2022, 20(9): 839-841.

[10]

田思岳. 肿瘤干细胞标志物CD44/SOX2在食管鳞癌中的临床病理意义及预测模型的构建[D]. 乌鲁木齐新疆医科大学, 2024.

[11]

张琳, 刘益娟, 郑建涛, 等. 胃癌患者Sox2蛋白和CTHRC-1蛋白的表达与肿瘤发展密切相关[J]. 基因组学与应用生物学, 2019, 38(2): 881-886.

[12]

Xie H Y, Yao J, Wang Y X, et al. Exosome-transmitted circVMP1 facilitates the progression and cisplatin resistance of non-small cell lung cancer by targeting miR-524-5p-METTL3/SOX2 axis[J]. Drug Deliv, 2022, 29(1): 1257-1271.

[13]

Zhu Y, Huang S M, Chen S Y, et al. SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer[J]. Cell Death Dis, 2021, 12: 449.

[14]

Blassberg R, Patel H, Watson T, et al. Sox2 levels regulate the chromatin occupancy of WNT mediators in epiblast progenitors responsible for vertebrate body formation[J]. Nat Cell Biol, 2022, 24(5): 633-644.

[15]

Duan H X, Liu Y H, Gao Z G, et al. Recent advances in drug delivery systems for targeting cancer stem cells[J]. Acta Pharm Sin B, 2021, 11(1): 55-70.

[16]

Kuo M H, Lee A C, Hsiao S H, et al. Cross-talk between SOX2 and TGFβ signaling regulates EGFR-TKI tolerance and lung cancer dissemination[J]. Cancer Res, 2020, 80(20): 4426-4438.

[17]

Bracht J W P, Karachaliou N, Berenguer J, et al. Osimertinib and pterostilbene in EGFR-mutation-positive non-small cell lung cancer (NSCLC)[J]. Int J Biol Sci, 2019, 15(12): 2607-2614.

[18]

Frampton J E. Osimertinib: a review in completely resected, early-stage, EGFR mutation-positive NSCLC[J]. Target Oncol, 2022, 17(3): 369-376.

[19]

Leonetti A, Sharma S, Minari R, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer[J]. Br J Cancer, 2019, 121(9): 725-737.

[20]

Schoenfeld A J, Arbour K C, Rizvi H, et al. Severe immune-related adverse events are common with sequential PD-(L)₁ blockade and osimertinib[J]. Ann Oncol, 2019, 30(5): 839-844.

[21]

Zeng J, Ding X J, Ding J H, et al. Histological transformation into SCLC: an important resistance mechanism of NSCLC upon immunotherapy[J]. Front Immunol, 2023, 14: 1275957.

[22]

Haratake N, Ozawa H, Morimoto Y, et al. MUC1-C is a common driver of acquired osimertinib resistance in NSCLC[J]. J Thorac Oncol, 2024, 19(3): 434-450.

[23]

Grazini U, Markovets A, Ireland L, et al. Overcoming osimertinib resistance with AKT inhibition in EGFRm-driven non-small cell lung cancer with PIK3CA/PTEN alterations[J]. Clin Cancer Res, 2024, 30(18): 4143-4154.

[24]

Zhao F Y, Chen M T, Wu T J, et al. Integration of single-cell and bulk RNA sequencing to identify a distinct tumor stem cells and construct a novel prognostic signature for evaluating prognosis and immunotherapy in LUAD[J]. J Transl Med, 2025, 23(1): 222.

[25]

Gardner E E, Earlie E M, Li K T, et al. Lineage-specific intolerance to oncogenic drivers restricts histological transformation[J]. Science, 2024, 383(6683): eadj1415.

[26]

Wang Z F, Li Z, Zhou K, et al. Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing[J]. Nat Commun, 2021, 12: 6500.

[27]

Li Z X, Zhuang X Q, Pan C H, et al. Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma[J]. Cancer Discov, 2024, 14(2): 308-325.

[28]

Lindsay M L, Vinay K K, Sai M, et al. Epigenomic state transitions characterize tumor progression in mouse lung adenocarcinoma[J]. Cancer Cell, 2020, 38(2): 212-228.

[29]

Sancho P, Barneda D, Heeschen C. Hallmarks of cancer stem cell metabolism[J]. Br J Cancer, 2016, 114(12): 1305-1312.

[30]

Prasetyanti P R, Medema J P. Intra-tumor heterogeneity from a cancer stem cell perspective[J]. Mol Cancer, 2017, 16(1): 41.

[31]

Han J Y, Won M, Kim J H, et al. Cancer stem cell-targeted bio-imaging and chemotherapeutic perspective[J]. Chem Soc Rev, 2020, 49(22): 7856-7878.

[32]

Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers[J]. Life Sci, 2019, 234: 116781.

[33]

He S H, Nakada D, Morrison S J. Mechanisms of stem cell self-renewal[J]. Annu Rev Cell Dev Biol, 2009, 25: 377-406.

[34]

Hu F, Li C H, Zheng X X, et al. Lung adenocarcinoma resistance to therapy with EGFR-tyrosine kinase inhibitors is related to increased expression of cancer stem cell markers SOX2, OCT4 and NANOG[J]. Oncol Rep, 2020, 43(2): 727-735.

[35]

Li L, Wang Y B, Jiao L, et al. Protective autophagy decreases osimertinib cytotoxicity through regulation of stem cell-like properties in lung cancer[J]. Cancer Lett, 2019, 452: 191-202.

2026年第36卷第7期

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文章信息

doi: 10.12048/j.issn.1674-229X.2026.07.004

接收时间：2025-11-04
首发时间：2026-10-27
出版时间：2026-07-25

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出版历史

收稿日期：2025-11-04

基金

中国博士后科学基金(2025M773584)

广东省医院药学研究基金——肿瘤支持治疗研究基金（复星基金）立项项目(2024A02010)

作者信息

中山大学附属第一医院药学部，广东　广州　510080

通讯作者:

唐可京，主任医师，研究方向：肺癌及其他呼吸性疾病，E-mail：tangkj@mail.sysu.edu.cn

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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