Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo

Ferrari,Silvia   Martina; Bocci,Guido; Di Desidero,Teresa; Ruffilli,Ilaria; Elia,Giusy; Ragusa,Francesca; Fioravanti,Anna; Orlandi,Paola; Paparo,Sabrina  Rosaria; Patrizio,Armando; Piaggi,Simona; La Motta,Concettina; Ulisse,Salvatore; Baldini,Enke; Materazzi,Gabriele; Miccoli,Paolo; Antonelli,Alessandro; Fallahi,Poupak

doi:10.3892/or.2018.6305

Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo

Authors:
- Silvia Martina Ferrari
- Guido Bocci
- Teresa Di Desidero
- Ilaria Ruffilli
- Giusy Elia
- Francesca Ragusa
- Anna Fioravanti
- Paola Orlandi
- Sabrina Rosaria Paparo
- Armando Patrizio
- Simona Piaggi
- Concettina La Motta
- Salvatore Ulisse
- Enke Baldini
- Gabriele Materazzi
- Paolo Miccoli
- Alessandro Antonelli
- Poupak Fallahi
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Affiliations: Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Ι‑56126 Pisa, Italy, Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, I‑56126 Pisa, Italy, Department of Pharmacy, University of Pisa, I‑56126 Pisa, Italy, Department of Surgical Sciences, ‘Sapienza’ University of Rome, I‑00161 Rome, Italy, Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, I‑56124 Pisa, Italy
Published online on: March 8, 2018 https://doi.org/10.3892/or.2018.6305
Pages: 2306-2314

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Abstract

The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice. Vandetanib significantly reduced ATC cell proliferation (P<0.01, ANOVA), induced apoptosis dose‑dependently (P<0.001, ANOVA), and inhibited migration (P<0.01) and invasion (P<0.001). Furthermore, vandetanib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in ATC cells. In 8305C and AF cells, vandetanib significantly inhibited the proliferation, inducing also apoptosis. 8305C cells were injected subcutaneously in CD nu/nu mice and tumor masses became detectable after 30 days. Vandetanib (25 mg/kg/day) significantly inhibited tumor growth and VEGF‑A expression and microvessel density in 8305C tumor tissues. In conclusion, the antitumor and antiangiogenic activity of vandetanib is very auspicious in ATC, opening the way to a future clinical evaluation.

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