Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REar-ranged 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 An-nexin 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 ana-lyzing the effects on the physiological development of the sub‐intestinal vein plexus and the tu-mor‐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. Regard-ing 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.

Vandetanib versus cabozantinib in medullary thyroid carcinoma: A focus on anti‐angiogenic effects in zebrafish model / S. Carra, G. Gaudenzi, A. Dicitore, D. Saronni, M.C. Cantone, A. Plebani, A. Ghilardi, M.O. Borghi, L.J. Hofland, L. Persani, G. Vitale. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:6(2021 Mar 16). [10.3390/ijms22063031]

Vandetanib versus cabozantinib in medullary thyroid carcinoma: A focus on anti‐angiogenic effects in zebrafish model

G. Gaudenzi
Secondo
;
A. Dicitore;D. Saronni;M.C. Cantone;A. Ghilardi;M.O. Borghi;L. Persani;G. Vitale
Ultimo
2021

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 REar-ranged 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 An-nexin 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 ana-lyzing the effects on the physiological development of the sub‐intestinal vein plexus and the tu-mor‐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. Regard-ing 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.
Angiogenesis; Cabozantinib; Medullary thyroid carcinoma (MTC); Tumor xenograft; Tyrosine kinase in-hibitors (TKIs); Vandetanib; Zebrafish; Angiogenesis Inhibitors; Anilides; Animals; Apoptosis; Carcinoma, Neuroendocrine; Cell Cycle; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Embryo, Nonmammalian; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Piperidines; Pyridines; Quinazolines; Thyroid Neoplasms; Zebrafish
Settore MED/13 - Endocrinologia
   From bed to benchside: untAngling THe molecular mechanisms of disease progressioN in neuroenDocRine nEoplAsMS (FAITH IN DREAMS)
   FAITH IN DREAMS
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017Z3N3YC_003
16-mar-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/849974
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