Related Experiment Video
Updated: Mar 26, 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
TGF-β1 induces erlotinib resistance in non-small cell lung cancer by down-regulating PTEN
Hua Shen1, Dan Guan1, Jianxin Shen2
1Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Background:
TKI-acquired resistance is a tough obstacle for effectively treating NSCLC patients with EGFR mutant characteristics. T790M mutations and MET amplifications account for 70% of the acquired resistance, but the causes for the remaining 30% need elucidation.
Methods:
We detected TGF-β1and PTEN expression levels in 51 NSCLC patients undergoing EGFR-TKI treatment using Immunohistochemistry (IHC) assay. We examined erlotinib sensitivity, apoptosis rate, and invasion ability in PC-9 cells and PC-9/TGF-β1 cells with CCK-8, flow cytometry, and trans-well assays. We examined and analyzed the AKT and ERK pathways' expression levels using western blot.
Results:
High TGF-β1 and low PTEN expression levels were correlated with poor EGFR-TKI sensitivity and overall survival in 51 NSCLC samples. In vitro analysis revealed that TGF-β1 could reduce erlotinib sensitivity, increase anti-apoptosis ability and invasive characteristic in TKI-sensitive PC-9 cell lines by down-regulating PTEN and activating the Akt and ERK pathways.
Conclusions:
The results suggest that TGF-β1 demonstrated another acquired erlotinib resistance by down-regulating PTEN expression.
Insights
Transforming growth factor beta 1 (TGF-β1) induces erlotinib resistance in non-small cell lung cancer (NSCLC) by decreasing phosphatase and tensin homolog (PTEN) expression, impacting patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Acquired resistance to tyrosine kinase inhibitors (TKIs) poses a significant challenge in treating EGFR-mutant non-small cell lung cancer (NSCLC).
- While T790M mutations and MET amplifications explain 70% of resistance, the mechanisms behind the remaining 30% require further investigation.
Purpose of the Study:
- To investigate the role of TGF-β1 and PTEN in acquired resistance to EGFR-TKIs in NSCLC.
- To elucidate the molecular mechanisms by which TGF-β1 influences erlotinib sensitivity and cellular behavior.
Main Methods:
- Immunohistochemistry (IHC) was used to assess TGF-β1 and PTEN expression in 51 NSCLC patients.
- In vitro assays (CCK-8, flow cytometry, trans-well) evaluated erlotinib sensitivity, apoptosis, and invasion in PC-9 and PC-9/TGF-β1 cells.
- Western blot analysis examined the activation of AKT and ERK pathways.
Main Results:
- High TGF-β1 and low PTEN expression correlated with reduced EGFR-TKI sensitivity and poorer survival in NSCLC patients.
- TGF-β1 exposure decreased erlotinib sensitivity, enhanced anti-apoptosis, and promoted invasion in TKI-sensitive PC-9 cells.
- TGF-β1 mediated these effects by down-regulating PTEN and activating the AKT and ERK signaling pathways.
Conclusions:
- TGF-β1 contributes to acquired erlotinib resistance in NSCLC.
- Down-regulation of PTEN expression by TGF-β1 is a key mechanism driving this resistance.
More Related Videos
09:38Establishing 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
13:34A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
Related Concept Videos
01:16TGF - β Signaling Pathway
02:38Mitogens and the Cell Cycle
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...