ArticleActa pharmacologica Sinica2024
Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.
Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 27 citations in OpenAlex.
- Triptolide Suppresses Tongue Squamous Cell Carcinoma Progression via PI3K-AKT Pathway Inhibition: An Integrative Network Pharmacology and Experimental Validation Study.The Kaohsiung journal of medical sciences · 2026Article
- Harnessing nanoparticles to unlock the therapeutic potential of triptolide in cancer treatment.Medical oncology (Northwood, London, England) · 2026Review
- Triptolide: A Narrative Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications.Cancers · 2026Review
- Loss of CA12 drive proliferation and fibrosis in type i congenital pulmonary airway malformation via promoting abnormal activation of SHH signaling.Cell communication and signaling : CCS · 2026Article
- Endothelial microparticles in high glucose environment: molecular pathways of GDM-associated placental dysfunction and coenzyme Q10-based targeted therapy.Journal of nanobiotechnology · 2026Article
- Triptolide in Combination with the Gli1 Inhibitor GANT61 Eradicates Anaplastic Thyroid Cancer by Suppressing Cancer Stem Cell Self-Renewal and Enhancing Apoptosis and Pyroptosis.International journal of biological sciences · 2026Article
- The Role of Hedgehog Signaling in Non-small Cell Lung Cancer: Targeting Tumor Invasion, Therapy Resistance and Novel Therapeutic Strategies.International journal of biological sciences · 2026Review
- VASN Enhances IGF2BP3 Stability via USP10 Deubiquitination to Promote Triple-negative Breast Cancer Paclitaxel Resistance.International journal of biological sciences · 2026Article
- HHIPL2 positively governs Hedgehog signaling to accelerate non-small cell lung cancer progression via enhancing HNRNPC-mediated HNF1A mRNA stabilization.Cell death & disease · 2025Article
- Intratumorally specific microbial-derived lipopolysaccharide contributes to non-small cell lung cancer progression.Virulence · 2025Article
- Natural compound triptolide induces caspase-3/GSDME-mediated pyroptosis by promoting ROS accumulation in small cell lung cancer.Cancer cell international · 2025Article
- Re-sensitization of cancer multidrug resistance through P-gp, MRP1 and BCRP modulation: advances in terpenoids based cancer therapy.Discover oncology · 2025Review
- TAIII Suppresses the Growth of T790M-Mutant Non-Small-Cell Lung Cancer by Targeting the EGFR/ERK Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Formation and evaluation of docetaxel and triptolide polymer micelles for anti-cancer activity.Nanomedicine (London, England) · 2025Article
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- Article
- Combination Therapy for Overcoming Multidrug Resistance in Breast Cancer Through Hedgehog Signaling Pathway Regulation.Pharmaceutics · 2025Article
- Exosomal circRNAs: key modulators in breast cancer progression.Cell death discovery · 2025Review
- Insights into emerging mechanisms of ferroptosis: new regulators for cancer therapeutics.Cell biology and toxicology · 2025Review
- Eupalinolide A inhibits cancer progression and induces ferroptosis and apoptosis by targeting the AMPK/mTOR/SCD1 signalling in non-small cell lung cancer.Frontiers in pharmacology · 2025Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.
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