ArticleThoracic cancer2020
M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR.
Article in Thoracic cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- The CCL2-CCR2 axis in primary lung cancer and pulmonary metastasis: from molecular mechanisms to therapeutic potentials.Frontiers in immunology · 2026Review
- Single-Cell RNA Sequencing in Unraveling Acquired Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: New Perspectives.International journal of molecular sciences · 2025Review
- Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review.Medicine · 2025Review
- The role of tumor-associated macrophages in lung cancer.Frontiers in immunology · 2025Review
- Fasting-mimicking diet enhances EGFR-TKI efficacy in oral cancer through dual mechanisms: direct cancer cell sensitization and tumor-associated macrophage crosstalk.Frontiers in pharmacology · 2025Article
- Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.MedComm · 2024Review
- CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway.Acta biochimica et biophysica Sinica · 2024Article
- Establishment of a novel microfluidic co-culture system for simultaneous analysis of multiple indicators of gefitinib sensitivity in colorectal cancer cells.Mikrochimica acta · 2024Article
- Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects.Frontiers in immunology · 2023Review
- Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance.Frontiers in genetics · 2023Review
- Review
- Identification of Master Regulators Driving Disease Progression, Relapse, and Drug Resistance in Lung Adenocarcinoma.Frontiers in bioinformatics · 2022Article
- Exosomal long non-coding RNA SOX2 overlapping transcript enhances the resistance to EGFR-TKIs in non-small cell lung cancer cell line H1975.Human cell · 2021Article
- MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe biological behavior of cells change after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. Here, we aimed to explore the changes in the biological behavior of tumors and to observe the differences in the release of cytokines and chemokines which can influence the tumor microenvironment. We also aimed to study how TKIs-resistant cell lines recruit macrophages to reduce the sensitivity of the cells following gefitinib administration.
methodsWe generated and maintained gefitinib-resistant cell lines to study the differences between gefitinib-sensitive cell lines according to clone formation, cell growth curve analysis, whole-exome sequencing, and qPCR ARRAY technology. We used the WNT/β-catenin inhibitor, WNT/β-catenin activator and overexpression β-catenin lentivirus to observe the changes in CCL2. M2 macrophages and gefitinib-resistant cell lines HCC827/GR were cocultured to detect the viability gefitinib for inducing cell death.
resultsThe proliferation and migratory activities were much more pronounced in HCC827/GR cells. CCL2 expression was also enhanced and regulated by β-catenin in HCC827/GR. CCL2 promoted the chemotactic ability of M2 macrophages. M2 macrophages reduced the antitumor effect of gefitinib treatment by activating AKT/mTOR.
conclusionsGefitinib-resistant cell lines have stronger proliferation and migration capabilities, and attract macrophages by releasing more CCL2 to reduce the sensitivity of cells to gefitinib.
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