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Updated: May 9, 2026
Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
High NOTCH activity induces radiation resistance in non small cell lung cancer
Jan Theys1, Sanaz Yahyanejad1, Roger Habets1
1Department of Radiation Oncology (MAASTRO Lab), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC+).
Background And Purpose:
Patients with advanced NSCLC have survival rates <15%. The NOTCH pathway plays an important role during lung development and physiology but is often deregulated in lung cancer, making it a potential therapeutic target. We investigated NOTCH signaling in NSCLC and hypothesized that high NOTCH activity contributes to radiation resistance.
Materials And Methods:
NOTCH signaling in NSCLC patient samples was investigated using quantitative RT-PCR. H460 NSCLC cells with either high or blocked NOTCH activity were generated and their radiation sensitivity monitored using clonogenic assays. In vivo, xenograft tumors were irradiated and response assessed using growth delay. Microenvironmental parameters were analyzed by immunohistochemistry.
Results:
Patients with high NOTCH activity in tumors showed significantly worse disease-free survival. In vitro, NOTCH activity did not affect the proliferation or intrinsic radiosensitivity of NSCLC cells. In contrast, xenografts with blocked NOTCH activity grew slower than wild type tumors. Tumors with high NOTCH activity grew significantly faster, were more hypoxic and showed a radioresistant phenotype.
Conclusions:
We demonstrate an important role for NOTCH in tumor growth and correlate high NOTCH activity with poor prognosis and radioresistance. Blocking NOTCH activity in NSCLC might be a promising intervention to improve outcome after radiotherapy.
Insights
High NOTCH pathway activity in non-small cell lung cancer (NSCLC) correlates with poor prognosis and radiation resistance. Blocking NOTCH may improve radiotherapy outcomes for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The NOTCH pathway is crucial for lung development but often dysregulated in non-small cell lung cancer (NSCLC).
- High NOTCH activity is implicated as a potential driver of therapeutic resistance in various cancers.
Purpose of the Study:
- To investigate the role of NOTCH signaling in NSCLC.
- To determine if high NOTCH activity contributes to resistance against radiotherapy in NSCLC.
Main Methods:
- Quantitative RT-PCR analyzed NOTCH signaling in NSCLC patient samples.
- In vitro clonogenic assays assessed radiation sensitivity of NSCLC cells with manipulated NOTCH activity.
- In vivo xenograft models evaluated tumor response to irradiation and microenvironmental factors.
Main Results:
- Patients with high tumor NOTCH activity exhibited significantly worse disease-free survival.
- While NOTCH activity did not alter intrinsic radiosensitivity in vitro, blocking it slowed xenograft tumor growth.
- High NOTCH activity was associated with faster tumor growth, increased hypoxia, and radioresistance in vivo.
Conclusions:
- NOTCH signaling plays a significant role in NSCLC tumor progression and radioresistance.
- High NOTCH activity is a biomarker for poor prognosis in NSCLC patients.
- Targeting NOTCH signaling presents a potential therapeutic strategy to enhance radiotherapy efficacy in NSCLC.
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