Rosmarinic acid potentiates gefitinib in lung adenocarcinoma by modulating interactions between cancer cells and cancer-associated fibroblasts
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View abstract on PubMed
Summary
This summary is machine-generated.Cancer-associated fibroblasts (CAFs) show a biphasic role in non-small cell lung cancer (NSCLC) progression. Rosmarinic acid (RA) modulates these interactions, enhancing gefitinib
Area Of Science
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background
- Cancer-associated fibroblasts (CAFs) are key players in tumor progression.
- The temporal dynamics of CAF-tumor cell interactions are not well understood.
- Non-small cell lung cancer (NSCLC) progression is influenced by CAFs.
Purpose Of The Study
- To investigate the time-dependent interactions between NSCLC cells and CAFs.
- To evaluate the potential of rosmarinic acid (RA) in modulating these interactions.
- To assess the therapeutic effects of RA, alone and in combination with gefitinib, in preclinical models.
Main Methods
- In vitro co-culture of HCC827 lung adenocarcinoma cells and MRC-5 fibroblasts.
- Assessment of CAF activation markers (α-SMA, FAP) and epithelial-mesenchymal transition (EMT).
- In vivo xenograft models with varying tumor-to-fibroblast ratios, evaluating tumor growth and RA/gefitinib efficacy.
Main Results
- Tumor-CAF interactions exhibit a biphasic pattern: initial suppression followed by accelerated tumor progression.
- CAF activation peaked by day 6, with maximal EMT marker expression in NSCLC cells by day 8.
- RA treatment reduced CAF activation and EMT, suppressed tumor growth in CAF-enriched xenografts, and enhanced gefitinib efficacy.
Conclusions
- CAFs play a temporally biphasic role in NSCLC, initially suppressing then promoting tumor progression.
- Rosmarinic acid effectively modulates tumor-stromal interactions and enhances gefitinib's anti-tumor effects.
- RA may offer a strategy to overcome gefitinib resistance in NSCLC.
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