ArticleJournal of cancer research and clinical oncology2023
Using a zebrafish xenograft tumor model to compare the efficacy and safety of VEGFR-TKIs.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Small Fish, Big Answers: Zebrafish and the Molecular Drivers of Metastasis.International journal of molecular sciences · 2025Review
- Systemic Treatment for Unresectable Hepatocellular Carcinoma: A Surgeon's Perspective.Journal of hepatocellular carcinoma · 2025Review
- Zebrafish as model system for the biological characterization of CK1 inhibitors.Frontiers in pharmacology · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
purposeWe constructed a zebrafish xenograft tumor model to compare and quantify the antiangiogenic efficacy and safety of nine vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), axitinib, lenvatinib, pazopanib, apatinib, cabozantinib, sunitinib, semaxanib, sorafenib, and regorafenib, in parallel.
methodsCT26 and GL261 tumor cells were implanted into the perivitelline space of Tg (flk1: eGFP) zebrafish to construct a xenograft tumor model. VEGFR-TKIs' antiangiogenic efficacy was quantified using AngioTool software, and the median effective dose (ED50) was calculated. The toxicity was evaluated by calculating the median lethal dose (LD50) and gross morphological changes. Cardiac toxicity was further assessed by heart rate, heart rhythm, the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and pericardial edema.
resultsUsing the zebrafish xenograft tumor model, we found that all nine VEGFR-TKIs exhibited antiangiogenic abilities, but the effectiveness of semaxanib was worse than that of other VEGFR-TKIs. Meanwhile, the zebrafish toxicity assay showed that all tested VEGFR-TKIs were associated with cardiac-related toxicity, especially apatinib and axitinib, which caused serious pericardial edema in zebrafish at relatively low concentrations. A narrow therapeutic window was found for most VEGFR-TKIs, and the simultaneous occurrence of toxic effects of semaxanib was recognized.
conclusionOur findings showed the potential of using a zebrafish xenograft tumor model to accelerate VEGFR-TKI screening and further the development of more efficient and less toxic VEGFR-TKIs.
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Registered trials
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