ArticleCellular oncology (Dordrecht, Netherlands)2024
Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFβ and Hedgehog signal pathway.
Article in Cellular oncology (Dordrecht, Netherlands), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Ozone Micro-Nano Bubbles Application Controls Disease Development and Maintains Quality of FreshJournal of fungi (Basel, Switzerland) · 2026Article
- Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC.Current gene therapy · 2025Article
- Astragaloside IV represses hepatocellular carcinoma progression by modulating HMGB1-ferroptosis axis.Discover oncology · 2025Article
- Tailoring traditional Chinese medicine in cancer therapy.Molecular cancer · 2025Review
- Biomarkers and immunotherapy in endometrial cancer: mechanisms and clinical applications.Frontiers in immunology · 2025Review
- Efficacy and safety of oral Chinese medicine combined with chemotherapy: a systematic review and network meta-analysis.Frontiers in pharmacology · 2025Review
- Astragalus Injection Modulates the Pharmacokinetics of Doxorubicin and CYP450 Enzymes.Current pharmaceutical design · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
purposeTaxol is the first-line chemo-drug for advanced non-small cell lung cancer (NSCLC), but it frequently causes acquired resistance, which leads to the failure of treatment. Therefore, it is critical to screen and characterize the mechanism of the taxol-resistance reversal agent that could re-sensitize the resistant cancer cells to chemo-drug.
methodThe cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance.
resultsASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFβ and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC.
conclusionsThese findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK-TGFβ, Hedgehog axis.
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