Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects
| Autor: | Tullio Florio, Gianluigi Zona, Adriana Bajetto, Marica Arvigo, Diego Criminelli Rossi, Gabriele Gaggero, Diego Ferone, Alessandro Prior, Federica Nista, Claudia Campana, Federico Gatto, Federica Barbieri, Jessica Amarù, Agnese Solari |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
GH4C1 cell line endocrine system Cancer Research Somatotropic cell 030209 endocrinology & metabolism lcsh:RC254-282 Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Receptor pasireotide Somatostatin receptor Chemistry Cell growth GH-secreting pituitary tumors lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Growth hormone secretion Pasireotide 030104 developmental biology Acromegaly Octreotide Somatostatin receptor ligands Oncology Cell culture somatostatin receptor ligands Cancer research acromegaly hormones hormone substitutes and hormone antagonists Intracellular octreotide |
| Zdroj: | Cancers Volume 13 Issue 8 Cancers, Vol 13, Iss 1816, p 1816 (2021) |
| ISSN: | 2072-6694 |
| Popis: | First-generation somatostatin receptor ligands (fg-SRLs), such as octreotide (OCT), represent the first-line medical therapy in acromegaly. Fg-SRLs show a preferential binding affinity for somatostatin receptor subtype-2 (SST2), while the second-generation ligand, pasireotide (PAS), has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). Whether PAS acts via SST2 in somatotroph tumors, or through other SSTs (e.g., SST5), is a matter of debate. In this light, the combined treatment OCT+PAS could result in additive/synergistic effects. We evaluated the efficacy of OCT and PAS (alone and in combination) on growth hormone (GH) secretion in primary cultures from human somatotroph tumors, as well as on cell proliferation, intracellular signaling and receptor trafficking in the rat GH4C1 cell line. The results confirmed the superimposable efficacy of OCT and PAS in reducing GH secretion (primary cultures), cell proliferation, cAMP accumulation and intracellular [Ca2+] increase (GH4C1 cells), without any additive effect observed for OCT+PAS. In GH4C1 cells, co-incubation with a SST2-selective antagonist reversed the inhibitory effect of OCT and PAS on cell proliferation and cAMP accumulation, while both compounds resulted in a robust internalization of SST2 (but not SST5). In conclusion, OCT and PAS seem to act mainly through SST2 in somatotroph tumor cells in vitro, without inducing any additive/synergistic effect when tested in combination. |
| Databáze: | OpenAIRE |
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