PUBLICATION
Efficacy of a novel second-generation somatostatin-dopamine chimera (TBR-065) in human medullary thyroid cancer: a preclinical study
- Authors
- Dicitore, A., Cantone, M.C., Gaudenzi, G., Saronni, D., Carra, S., Borghi, M.O., Albertelli, M., Ferone, D., Hofland, L.J., Persani, L., Vitale, G.
- ID
- ZDB-PUB-201021-6
- Date
- 2020
- Source
- Neuroendocrinology 111(10): 937-950 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Antineoplastic Agents/pharmacology*
- Carcinoma, Neuroendocrine/drug therapy*
- Cell Line, Tumor
- Dopamine/analysis*
- Humans
- Somatostatin/analysis*
- Thyroid Neoplasms/drug therapy*
- PubMed
- 33075795 Full text @ Neuroendocrinology
Citation
Dicitore, A., Cantone, M.C., Gaudenzi, G., Saronni, D., Carra, S., Borghi, M.O., Albertelli, M., Ferone, D., Hofland, L.J., Persani, L., Vitale, G. (2020) Efficacy of a novel second-generation somatostatin-dopamine chimera (TBR-065) in human medullary thyroid cancer: a preclinical study. Neuroendocrinology. 111(10):937-950.
Abstract
Introduction Somatostatin and dopamine receptors have a pivotal role in control of hormone secretion and cell proliferation in different neuroendocrine neoplasms, including medullary thyroid cancer (MTC). In the present preclinical study, we evaluated the antitumor activity of TBR-065 (formerly BIM-23B065), a second-generation somatostatin-dopamine chimera, in two human MTC cell lines.
Methods the effects of lanreotide (LAN) and TBR-065 on the cell growth proliferation, calcitonin secretion, cell cycle, apoptosis, cell migration and tumor-induced angiogenesis have been evaluated through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, ECLIA assay, wound-healing assay and zebrafish platform, respectively.
Results TBR-065 exerted a more prominent antitumor activity compared to LAN in both MTC cell lines, as shown by inhibition of cell proliferation (maximal inhibition in TT: -50.3% and -37.6%, respectively; in MZ-CRC-1: -58.8% and -27%, respectively) and migration (in TT: -42.7% and -22.9%, respectively; in MZ-CRC-1: -75.5% and -58.2%, respectively). Only the new chimera decreased significantly the fraction of cells in S phase (TT: -33.8%, MZ-CRC-1: -18.8%), and increased cells in G2/M phase (TT: +13%, MZ-CRC-1: +30.5%). In addition, TBR-065 exerted a more prominent pro-apoptotic effect compared to LAN in TT cells. A concomitant decrease of calcitonin secretion was observed after 2 days of incubation with both drugs, with a more relevant effect of TBR-065. However, neither LAN nor TBR-065 showed any effect on tumor-induced angiogenesis, as evaluated using a zebrafish/tumor xenograft model.
Discussion/conclusion In MTC cell lines a second generation somatostatin-dopamine analogue, TBR-065, exerts a more relevant anti-tumor activity, as compared with LAN, through modulation of cell cycle, induction of apoptosis and reduction in migration. Further studies are required to establish whether TBR-065 has comparable potent inhibitory effects on tumor growth in vivo.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
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