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Updated: Jun 10, 2026

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
[Relationship between Mutations of the Epidermal Growth Factor Receptor Gene and Drug-Resistance to Gefitinib in
1Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Background:
To explore cell lines' difference of drug-resistance to gefitinib and the underlying mechanism.
Methods:
Human lung cancer cell lines of PC9, PC9/AB2, PC9/AB11, PC9/BB4 were treated in vitro, exons 18-21 of EGFR gene were sequenced and EGFR gene mRNA levels were measured.
Results:
Four cell lines' drug resistance difference of gefitinib were validated. All the four cell lines had the 15 bp deletion at exon 19, and AB11 had A to G point-mutation at exon 20. PC9 EGFR gene in the sensitive cell line was expressed much higher than that in 3 resistance cell lines by real-time PCR.
Conclusions:
There is significant difference of drug-resistance to gefitinib existed among the lung cancer cell lines PC9, PC9/AB2, PC9/AB11 and PC9/BB4. The mutations changes of expressive level of EGFR gene might be correlated with the acquired drug-resistance to gefitinib in lung cancer cell lines.
Insights
Lung cancer cell lines show varying resistance to gefitinib. EGFR gene mutations and expression levels correlate with this acquired drug resistance, impacting treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Gefitinib is a targeted therapy for non-small cell lung cancer (NSCLC).
- Understanding drug resistance mechanisms is crucial for optimizing NSCLC treatment.
- Cell line models are essential for studying drug response and resistance.
Purpose:
- To investigate differential gefitinib drug resistance among human lung cancer cell lines.
- To elucidate the molecular mechanisms underlying gefitinib resistance.
- To correlate EGFR gene alterations with gefitinib sensitivity/resistance.
Summary:
- Four lung cancer cell lines (PC9, PC9/AB2, PC9/AB11, PC9/BB4) were analyzed for gefitinib resistance.
- EGFR gene sequencing revealed a 15 bp deletion in exon 19 in all lines and an A-to-G mutation in exon 20 in PC9/AB11.
- Real-time PCR showed significantly higher EGFR mRNA levels in the gefitinib-sensitive PC9 cell line compared to resistant lines.
Impact:
- Identifies distinct gefitinib resistance profiles in lung cancer cell lines.
- Suggests a correlation between EGFR gene mutations, expression levels, and acquired gefitinib resistance.
- Provides a basis for further research into overcoming gefitinib resistance in NSCLC.
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