Abstract
PurposeFirst-generation somatostatin analogs, octreotide (OCT) and lanreotide, are the cornerstone for the medical treatment of growth hormone (GH)-secreting pituitary tumors. A new multireceptor analog, such as pasireotide (PAS), showed better activity than OCT in long-term treatment of patients with acromegaly, but modulation of intracellular key processes is still unclear in vitro. In this study, we evaluated the antitumor activity of OCT and PAS in two GH-secreting pituitary tumor cell lines, GH3 and GH4C1, after a long-term incubation.MethodsThe effects of PAS and OCT on the cell viability, cell cycle, apoptosis, GH secretion, and tumor-induced angiogenesis have been evaluated through a colorimetric method (MTS Assay), DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, ELISA assay and zebrafish platform, respectively.ResultsPAS showed a more potent antitumor activity compared to OCT in GH3 cell line exerted through inhibition of cell viability, perturbation of cell cycle progression, and induction of apoptosis after 6 days of incubation. A concomitant decrease in GH secretion has been observed after 2 days of incubation only with PAS. No effect on tumor-induced angiogenesis has been reported after treatment with OCT or PAS in zebrafish/tumor xenograft model.ConclusionLong-term incubation with PAS showed a more potent antitumor activity than that reported after OCT in GH3 cells, mainly modulated by a cell cycle perturbation and a relevant induction in apoptosis.
Highlights
Growth hormone (GH)-secreting pituitary tumors account for about 30% of all functioning pituitary tumors
We evaluated the mRNA expression of S ST1, SST2, SST3, SST4 and SST5 in GH3 and GH4C1 cells by TD-PCR
This study evaluated the long-term effects of different Somatostatin receptor ligands (SRLs) on GH-secreting pituitary tumor cell lines, supporting a more potent anti-tumor effect of PAS than OCT
Summary
Growth hormone (GH)-secreting pituitary tumors account for about 30% of all functioning pituitary tumors. Somatostatin receptor ligands (SRLs) selective for S ST2, such as octreotide (OCT) and lanreotide, are the cornerstone for the medical therapy of these tumors [4, 5]. Long-term treatment of acromegaly with OCT and lanreotide has been widely studied and showed normalization of GH and IGF-1 levels in about 20–70% and tumor shrinkage in 36–75% of patients [6,7,8,9]. A relevant group of patients showed partial or total resistance to SRLs [10]. This phenomenon is probably due to the absence, reduced density, genetic aberration or desensitization of SSTs [11,12,13]. Pasireotide (PAS), a novel SRL with multireceptor-binding profile, has been recently used
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