Octreotide and pasireotide combination treatment in somatotroph tumor cells: Predominant role of sst2 in mediating ligand effects

Jessica Amarù, Federica Barbieri, Marica Arvigo, Agnese Solari, Adriana Bajetto, Federica Nista, Claudia Campana, Gabriele Gaggero, Alessandro Prior, Diego Criminelli Rossi, Gianluigi Zona, Diego Ferone, Tullio Florio, Federico Gatto

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1816
Issue number8
Publication statusPublished - Apr 2 2021


  • Acromegaly
  • GH-secreting pituitary tumors
  • GH4C1 cell line
  • Octreotide
  • Pasireotide
  • Somatostatin receptor ligands

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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