ArticlePharmacological research2022
The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition.
Article in Pharmacological research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Phytochemicals Modulating Receptor Tyrosine Kinase Signaling Networks in Endometriosis.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- Inhibition of PGC1β-dependent mitochondrial biogenesis enhances EGFR-targeted therapy in lung cancer.EMBO molecular medicine · 2026Article
- Cellular and Molecular Mechanisms of Berberine in Cancer Therapy: Recent Advances.Archiv der Pharmazie · 2026Review
- Eugenol as a game-changer: overcoming osimertinib resistance in non-small cell lung cancer by inhibiting glycolysis via the tripartite motif containing 59/extracellular signal-regulated kinase pathway.Anti-cancer drugs · 2026Article
- Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Experimental and clinical insights into the therapeutic potential of Berberis vulgaris and its bioactive constituents in respiratory, allergic, and immunological disorders: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Natural compounds for non-small cell lung cancer treatment: focus on the EGFR signaling pathway.Frontiers in pharmacology · 2026Review
- Targeting MKK3/c-Myc interaction to overcome osimertinib acquired resistance in EGFR mutant lung cancer.Cancer letters · 2025Article
- Roles of Selected Bioactive Compounds in Inhibiting the Development and Progression of Cancer-A Review.International journal of molecular sciences · 2025Review
- The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.Current issues in molecular biology · 2025Review
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- A pan-cancer analysis of the oncogenic and immunological roles of RGS5 in clear cell renal cell carcinomas based on in vitro experiment validation.Human genomics · 2025Article
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- Advance in identified targets of berberine.Frontiers in pharmacology · 2025Review
- Development of Traditional Chinese Medicine in combination with EGFR Inhibitors against Cancer.Journal of Cancer · 2025Review
- Pharmacological properties and therapeutic potential of berberine: a comprehensive review.Frontiers in pharmacology · 2025Review
- Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy.Military Medical Research · 2024Review
- Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer.The Journal of experimental medicine · 2024Article
- IL-22: A key inflammatory mediator as a biomarker and potential therapeutic target for lung cancer.Heliyon · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Berberine is a natural product that has long been used in traditional Chinese medicine due to its antimicrobial, anti-inflammatory and metabolism-regulatory properties. Osimertinib is the first third-generation EGFR-tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancer (NSCLC) with activating EGFR mutations and those resistant to earlier generation EGFR-TKIs due to a T790M mutation. However, emergence of acquired resistance to osimertinib limits its long-term efficacy in the clinic. One known mechanism of acquired resistance to osimertinib and other EGFR-TKIs is MET (c-MET) gene amplification. Here, we report that berberine, when combined with osimertinib, synergistically and selectively decreased the survival of several MET-amplified osimertinib-resistant EGFR mutant NSCLC cell lines with enhanced induction of apoptosis likely through Bim elevation and Mcl-1 reduction. Importantly, this combination effectively enhanced suppressive effect on the growth of MET-amplified osimertinib-resistant xenografts in nude mice and was well tolerated. Molecular modeling showed that berberine was able to bind to the kinase domain of non-phosphorylated MET, occupy the front of the binding pocket, and interact with the activation loop, in a similar way as other known MET inhibitors do. MET kinase assay showed clear concentration-dependent inhibitory effects of berberine against MET activity, confirming its kinase inhibitory activity. These findings collectively suggest that berberine can act as a naturally-existing MET inhibitor to synergize with osimertinib in overcoming osimertinib acquired resistance caused by MET amplification.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.