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Updated: Aug 15, 2025
Generation of Zebrafish Larval Xenografts and Tumor Behavior Analysis
Published on: June 19, 2021
Using a zebrafish xenograft tumor model to compare the efficacy and safety of VEGFR-TKIs
Hou Wanting1, Zhong Jian2, Xiao Chaoxin2
1Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
Purpose:
We 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.
Methods:
CT26 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.
Results:
Using 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.
Conclusion:
Our 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.
Insights
A novel zebrafish model effectively screened nine vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) for antiangiogenic efficacy and cardiac toxicity. This model aids in developing safer, more effective VEGFR-TKIs.
Area of Science:
- Oncology
- Pharmacology
- Toxicology
Background:
- Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) are crucial in cancer therapy.
- Assessing the antiangiogenic efficacy and safety of multiple VEGFR-TKIs requires efficient preclinical models.
Purpose of the Study:
- To establish and utilize a zebrafish xenograft tumor model for parallel comparison of antiangiogenic efficacy and safety of nine VEGFR-TKIs.
- To quantify the median effective dose (ED50) and median lethal dose (LD50) for selected VEGFR-TKIs.
Main Methods:
- Constructed a zebrafish xenograft tumor model using CT26 and GL261 cells in Tg (flk1: eGFP) zebrafish.
- Quantified antiangiogenic efficacy using AngioTool software and calculated ED50.
- Evaluated toxicity via LD50, morphological changes, and detailed cardiac assessments (heart rate, rhythm, SV-BA distance, pericardial edema).
Main Results:
- All nine VEGFR-TKIs demonstrated antiangiogenic properties, with semaxanib showing lower efficacy.
- All tested VEGFR-TKIs induced cardiac toxicity, notably apatinib and axitinib causing severe pericardial edema at low doses.
- Most VEGFR-TKIs exhibited a narrow therapeutic window, and semaxanib presented simultaneous toxic effects.
Conclusions:
- The zebrafish xenograft tumor model is a valuable tool for rapid screening of VEGFR-TKIs.
- This model facilitates the development of VEGFR-TKIs with improved efficacy and reduced toxicity profiles.
