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Updated: May 19, 2026
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Isolation and characterization of erlotinib-resistant human non-small cell lung cancer A549 cells
Ryuji Ikeda1, Lee C Vermeulen, Elim Lau
1Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Abstract:
Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an effective therapy for non-small cell lung cancer (NSCLC). However, resistance to erlotinib reduces its efficacy. To investigate the basis of erlotinib resistance, we isolated erlotinib-resistant human NSCLC A549 cells, termed A549/ER cells. The A549/ER cells were found to be resistant to erlotinib, as well as paclitaxel and gemcitabine. We then performed a PCR array to investigate the resistance to erlotinib in A549/ER cells. EGFR expression in A549/ER cells was decreased compared to A549 cells. The expression of fibroblast growth factor 2 (FGF2) and p21 in A549/ER was increased when compared to A549 cells. Our results suggest that the down-regulation of EGFR and up-regulation of FGF2 is related to resistance to erlotinib in A549/ER cells.
Insights
Investigating erlotinib resistance in non-small cell lung cancer (NSCLC) revealed that resistant cells showed decreased epidermal growth factor receptor (EGFR) and increased fibroblast growth factor 2 (FGF2) expression, suggesting a link to treatment failure.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Erlotinib is a targeted therapy for non-small cell lung cancer (NSCLC) that inhibits the epidermal growth factor receptor (EGFR).
- Acquired resistance to erlotinib limits its long-term clinical efficacy in NSCLC patients.
- Understanding the molecular mechanisms of resistance is crucial for developing strategies to overcome treatment failure.
Purpose of the Study:
- To investigate the molecular basis of erlotinib resistance in human NSCLC cells.
- To identify potential biomarkers associated with erlotinib resistance.
Main Methods:
- Generation of erlotinib-resistant NSCLC cell line (A549/ER) from parental A549 cells.
- Assessment of cross-resistance to other chemotherapeutic agents (paclitaxel, gemcitabine).
- Utilized PCR array to analyze gene expression changes in resistant cells compared to sensitive cells.
Main Results:
- A549/ER cells exhibited resistance not only to erlotinib but also to paclitaxel and gemcitabine.
- Compared to A549 cells, A549/ER cells showed significantly decreased EGFR expression.
- Expression of fibroblast growth factor 2 (FGF2) and p21 was notably increased in A549/ER cells.
Conclusions:
- Down-regulation of EGFR and up-regulation of FGF2 are potentially associated with erlotinib resistance in NSCLC.
- These molecular alterations may contribute to the acquired resistance phenotype observed in A549/ER cells.
- Further research is warranted to validate these findings and explore therapeutic implications.
