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Published on: April 6, 2016
Tanreqing injection inhibits stemness and enhances sensitivity of non-small cell lung cancer models to gefitinib
Zhenzhen Xiao1,2, Lina Ding2, Yaya Yu1,2
1Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China.
Abstract:
Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has emerged as a significant obstacle in managing patients with EGFR-mutant non-small-cell lung cancer (NSCLC), necessitating the exploration of novel therapeutic approaches. Tanreqing injection (TRQ) is a kind of Chinese patent medicine known for its heat-clearing and detoxifying properties. Studies have shown a correlation between tumor drug resistance and enrichment of cancer stem cells (CSCs). We aim to investigate the feasibility of TRQ enhancing sensitivity to gefitinib by targeting CSCs and reactive oxygen species (ROS). In our study, TRQ significantly inhibited cell proliferation in gefitinib-resistant non-small-cell lung cancer (NSCLC) models including 2D cell lines, 3D cell spheres, tumor-bearing animal and organoids. Compared with the gefitinib group alone, addition of TRQ elevated ROS levels, attenuated upregulation of the protein levels of sex-determining region Y-box 2 (SOX2) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) induced by gefitinib treatment, and inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Scavenging ROS could restore tumor stemness, attenuate the inhibitory effect on the phosphorylation of STAT3, and promote cell proliferation. These results suggested that TRQ could enhance sensitivity of NSCLC models to gefitinib, providing a new combined treatment strategy.
Insights
Tanreqing injection (TRQ) enhances gefitinib sensitivity in non-small-cell lung cancer (NSCLC) by targeting cancer stem cells (CSCs) and reactive oxygen species (ROS). This combination therapy offers a novel strategy for overcoming EGFR-TKI resistance in NSCLC patients.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is a major challenge in treating EGFR-mutant non-small-cell lung cancer (NSCLC).
- Cancer stem cells (CSCs) are implicated in acquired drug resistance.
- Tanreqing injection (TRQ), a traditional Chinese medicine, possesses heat-clearing and detoxifying properties.
Purpose of the Study:
- To investigate if TRQ can enhance gefitinib sensitivity in NSCLC by targeting CSCs and reactive oxygen species (ROS).
- To explore the underlying mechanisms of TRQ's action in overcoming gefitinib resistance.
Main Methods:
- Utilized gefitinib-resistant NSCLC models, including 2D cell lines, 3D cell spheres, tumor-bearing animals, and organoids.
- Assessed cell proliferation, ROS levels, CSC markers (SOX2, ALDH1A1), and STAT3 phosphorylation.
- Investigated the role of ROS by employing ROS scavenging techniques.
Main Results:
- TRQ significantly inhibited proliferation in gefitinib-resistant NSCLC models.
- TRQ elevated ROS levels and attenuated the gefitinib-induced upregulation of SOX2 and ALDH1A1.
- TRQ inhibited STAT3 phosphorylation; ROS scavenging reversed these effects and promoted proliferation.
Conclusions:
- TRQ enhances gefitinib sensitivity in NSCLC models, suggesting a potential role in overcoming EGFR-TKI resistance.
- The mechanism involves increasing ROS levels, reducing CSC markers, and inhibiting STAT3 phosphorylation.
- TRQ combined with gefitinib represents a promising therapeutic strategy for NSCLC.
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