ArticleJournal of cellular and molecular medicine2021
Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms.Nutrients · 2024Pooled it
- AFP confers the resistance of lenvatinib in hepatocellular carcinoma by activating PI3K/AKT/LDHA signaling axis.Discover oncology · 2026Article
- Targeting DDOST improves the efficacy of lenvatinib and immunotherapy in hepatocellular carcinoma.Experimental & molecular medicine · 2025Article
- Novel combination therapy with phenformin enhances the effects of lenvatinib in hepatocellular carcinoma via AMPK-mediated PDGFRβ degradation.Cancer cell international · 2025Article
- Hepatocellular carcinoma drug resistance models.Cancer cell international · 2025Review
- Mechanisms of drug resistance in hepatocellular carcinoma.Biological procedures online · 2025Review
- Targeted inhibition of PDGFRA with avapritinib, markedly enhances lenvatinib efficacy in hepatocellular carcinoma in vitro and in vivo: clinical implications.Journal of experimental & clinical cancer research : CR · 2025Article
- Anti-Bacterial and Anti-Inflammatory Properties of Sophoridine and Its Effect on Diarrhea in Mice.International journal of molecular sciences · 2025Article
- Regulated Cell Death in Lenvatinib Resistance of Hepatocellular Carcinoma: from Molecular Mechanisms to Therapeutic Strategies.International journal of biological sciences · 2025Review
- Targeted therapy for liver cancer: Current status and future directions.BioImpacts : BI · 2025Review
- Identification of Key Genes and Pathways in Lenvatinib-resistant Hepatocellular Carcinoma using Bioinformatic Analysis and Experimental Validation.Current medicinal chemistry · 2025Article
- Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Journal of hematology & oncology · 2024Review
- CuET overcomes regorafenib resistance by inhibiting epithelial-mesenchymal transition through suppression of the ERK pathway in hepatocellular carcinoma.Translational oncology · 2024Article
- Article
- Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways.iScience · 2024Article
- Modulation of hypoxia-inducible factor-1 signaling pathways in cancer angiogenesis, invasion, and metastasis by natural compounds: a comprehensive and critical review.Cancer metastasis reviews · 2024Review
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Sophoridine Counteracts Obesity via Src-Mediated Inhibition of VEGFR Expression and PI3K/AKT Phosphorylation.International journal of molecular sciences · 2024Article
- Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).American journal of cancer research · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal cancer types with insufficient approved therapies, among which lenvatinib is a newly approved multi-targeted tyrosine kinase inhibitor for frontline advanced HCC treatment. However, resistance to lenvatinib has been reported in HCC treatment recently, which limits the clinical benefits of lenvatinib. This study aims to investigate the underlying mechanism of lenvatinib resistance and explore the potential drug to improve the treatment for lenvatinib-resistant (LR) HCC. Here, we developed two human LR HCC cell lines by culturing with long-term exposure to lenvatinib. Results showed that the vascular endothelial growth factor receptors (VEGFR)2 expression and its downstream RAS/MEK/ERK signalling were obviously up-regulated in LR HCC cells, whereas the expression of VEGFR1, VEGFR3, FGFR1-4 and PDGFRα/β showed no difference. Furthermore, ETS-1 was identified to be responsible for VEGFR2 mediated lenvatinib resistance. The cell models were further used to explore the potential strategies for restoration of sensitivity of lenvatinib. Sophoridine, an alkaloid extraction, inhibited the proliferation, colony formation, cell migration and increased apoptosis of LR HCC cells. In vivo and in vitro results showed Sophoridine could further sensitize the therapeutic of lenvatinib against LR HCC. Mechanism studies revealed that Sophoridine decreased ETS-1 expression to down-regulate VEGFR2 expression along with downstream RAS/MEK/ERK axis in LR HCC cells. Hence, our study revealed that up-regulated VEGFR2 expression could be a predicator of the resistance of lenvatinib treatment against HCC and provided a potential candidate to restore the sensitivity of lenvatinib for HCC treatment.
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