Related Experiment Video
Updated: Jun 24, 2026
In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts
Published on: August 14, 2019
Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
Silvia Carra1, Germano Gaudenzi2, Alessandra Dicitore2
1Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, 20095 Cusano Milanino, MI, Italy.
Abstract:
Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP) transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.
Insights
Vandetanib (VAN) and cabozantinib (CAB) show similar anti-cancer effects in medullary thyroid carcinoma (MTC) cells. However, cabozantinib (CAB) demonstrates stronger anti-angiogenic activity in preclinical models.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Medullary thyroid carcinoma (MTC) is a rare cancer originating from thyroid C cells.
- Vandetanib (VAN) and cabozantinib (CAB) are approved tyrosine kinase inhibitors for advanced MTC, targeting RET and other kinases.
- Comparative analysis of VAN and CAB's anti-tumor efficacy is crucial for optimizing treatment strategies.
Purpose of the Study:
- To compare the in vitro and in vivo anti-tumor activities of VAN and CAB in medullary thyroid carcinoma (MTC).
- To evaluate the effects of VAN and CAB on MTC cell viability, cell cycle, and apoptosis.
- To assess the anti-angiogenic potential of VAN and CAB using a zebrafish model.
Main Methods:
- In vitro: MTT assay for viability, flow cytometry for cell cycle and apoptosis in TT and MZ-CRC-1 MTC cells.
- In vivo: Zebrafish (Tg(fli1a:EGFP)) model to evaluate anti-angiogenic effects on sub-intestinal vein plexus and tumor xenografts.
- Dose-dependent analysis of drug effects on angiogenesis.
Main Results:
- VAN and CAB exhibited comparable inhibition of MTC cell viability and cell cycle progression.
- Both drugs induced apoptosis, with VAN showing a stronger effect in MZ-CRC-1 cells and CAB in TT cells.
- Both VAN and CAB demonstrated dose-dependent inhibition of angiogenesis in zebrafish, with CAB showing more potent activity.
Conclusions:
- VAN and CAB possess similar antiproliferative effects against MTC cells in vitro.
- Cabozantinib (CAB) exhibits a more significant anti-angiogenic effect compared to Vandetanib (VAN).
- These findings suggest distinct mechanisms of action and highlight CAB's potent anti-angiogenic properties in MTC treatment contexts.
