在非小细胞肺癌中,CCL2通过AKT-EMT通路促进EGFR-TKI耐药性

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Updated: Jun 22, 2025

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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

Yunlian Diao^1,2, Shibo Huang³, Fangpeng Liu²

¹Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, Jiangxi Medical Center for Major Public Health Events, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.

Acta biochimica et biophysica Sinica

|July 4, 2024

概括

化学基因连接体2 (CCL2) 驱动非小细胞肺癌 (NSCLC) 中对EGFR氨酸激酶抑制剂 (EGFR-TKI) 获得的耐药性. 抑制CCL2可以克服这种抵抗,并通过向AKT-表皮-介质酶过渡通路来减少癌细胞迁移.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症研究癌症研究

背景情况:

对EGFR氨酸激酶抑制剂 (EGFR-TKI) 获得的耐药性是非小细胞肺癌 (NSCLC) 治疗的一个主要挑战.
化学基因 (C-C 基因) 配体2 (CCL2) 已成为影响抗癌治疗结果的关键因素.
在NSCLC中EGFR-TKI耐药性的发展中CCL2的确切作用仍然不完全理解.

研究的目的:

在NSCLC细胞中对EGFR-TKI获得的耐药性中研究CCL2的功能和机制.
为了确定CCL2调制是否可以逆转EGFR-TKI抵抗.
阐明参与CCL2-介导抗性的信号通路.

主要方法:

对EGFR-TKI耐药NSCLC细胞中CCL2表达的分析.
在CCL2操纵 (抑制或淘汰) 后对EGFR-TKIs的敏感性评估.
评价细胞迁移和上皮层-介质细胞过渡 (EMT) 标志物.
对AKT-EMT信号通路的研究.

主要成果:

在EGFR-TKI抗性NSCLC细胞中发现CCL2异常上调,与对EGFR-TKI敏感性降低相关.
使用邦达里特或siRNA抑制CCL2,逆转EGFR-TKI耐药性,减少细胞迁移和EMT标志物表达.
CCL2上调促进了细胞迁移和EMT,这取决于AKT-EMT信号通路.

结论:

在NSCLC中,CCL2在促进对EGFR-TKIs获得的耐药性方面发挥着重要作用.
通过AKT信号通路,CCL2有助于增加细胞迁移和EMT.
向CCL2是一种潜在的治疗策略,可以克服NSCLC中的EGFR-TKI耐药性.

关键词:

在CCL2中,我们可以使用CCL2.对于EGFR-TKIs的耐药性,我们有所作为.表皮细胞-介质细胞过渡.非小细胞肺癌的肺癌.

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