ArticleJournal of traditional and complementary medicine2026
Huang-qin decoction increases the sensitivity of EGFR-TKIs to NSCLC cells by regulating stat3/GPX4 to induce redox ratio and ROS to inhibit CSCs.
Article in Journal of traditional and complementary medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: Our aim is to explore the combined effects and the potential mechanism between Huang-qin decoction (HQD) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) cells Methods: Ultra-high performance liquid chromatography (UPLC) was done to detect the consistency of ingredients in different batches of HQD. Cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay and Annexin V-FITC/PI assay were performed to detect the anti-cancer effects of HQD and EGFR-TKIs (1st generation EGFR-TKI gefitinib or 3rd generation EGFR-TKI Osimertinib) in different NSCLC cell lines. ATP assay was applied to detect the effect of HQD and EGFR-TKIs in NSCLC cell lines and organoids in three-dimensional (3D) culture. The mRNA expression levels of lung cancer stem cell markers makers and redox related genes, such as sex determining region Y-box 2 (SOX2), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), glutathione peroxidase 4 (GPX4), dual oxidase 1 (DUOX1) and dual oxidase 2 (DUOX2), were detected by using quantitative real-time PCR assay. Western blot methods were done to detect the effects of EGFR-TKIs and HQD on the protein expression levels of SOX2, ALDH1A1, GPX4, signal transducer and activator of transcription 3 (stat3) and p-stat3. Besides, the alteration of intracellular total reactive oxygen species (ROS) levels of NSCLC cells in 2D culture and 3D culture after the treatments were detected using DCFH-DA staining assay and fluorimetric intracellular total ROS activity assay, respectively. Femtosecond laser labeling free imaging (FLI) method was used to detect the redox ratio of NSCLC cells in 3D culture. Results: The consistency of ingredients in different batches of HQD was confirmed. HQD enhanced the anti-proliferation and pro-apoptosis effect of gefitinib or Osimertinib in NSCLC cell lines and organoids both in 2D culture and 3D culture Conclusions: HQD enhances the anti-cancer effect of EGFR-TKIs in NSCLC through ROS-mediated CSC makers inhibition by suppressing stat3/GPX4 axis to induce redox ratio, providing a novel strategy for the treatment of NSCLC patients.
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