PUBLICATION
Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
- Authors
- Carra, S., Gaudenzi, G., Dicitore, A., Saronni, D., Cantone, M.C., Plebani, A., Ghilardi, A., Borghi, M.O., Hofland, L.J., Persani, L., Vitale, G.
- ID
- ZDB-PUB-210407-53
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(6): (Journal)
- Registered Authors
- Ghilardi, Anna
- Keywords
- angiogenesis, cabozantinib, medullary thyroid carcinoma (MTC), tumor xenograft, tyrosine kinase inhibitors (TKIs), vandetanib, zebrafish
- MeSH Terms
-
- Angiogenesis Inhibitors/therapeutic use*
- Anilides/pharmacology
- Anilides/therapeutic use*
- Animals
- Apoptosis/drug effects
- Carcinoma, Neuroendocrine/blood supply
- Carcinoma, Neuroendocrine/drug therapy*
- Carcinoma, Neuroendocrine/pathology
- Cell Cycle/drug effects
- Cell Line, Tumor
- Cell Survival/drug effects
- Disease Models, Animal
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/drug effects
- Humans
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Physiologic/drug effects
- Piperidines/therapeutic use*
- Pyridines/pharmacology
- Pyridines/therapeutic use*
- Quinazolines/therapeutic use*
- Thyroid Neoplasms/blood supply
- Thyroid Neoplasms/drug therapy*
- Thyroid Neoplasms/pathology
- Zebrafish/embryology
- Zebrafish/physiology*
- PubMed
- 33809722 Full text @ Int. J. Mol. Sci.
Citation
Carra, S., Gaudenzi, G., Dicitore, A., Saronni, D., Cantone, M.C., Plebani, A., Ghilardi, A., Borghi, M.O., Hofland, L.J., Persani, L., Vitale, G. (2021) Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model. International Journal of Molecular Sciences. 22(6):.
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)y1 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping