Pasireotide, a somatostatin analog, is reported to have anti-proliferative effects in neuroendocrine tumors (NETs). We therefore assessed the efficacy of pasireotide, for treating pancreatic and pituitary NETs that develop in a mouse model of Multiple Endocrine Neoplasia Type 1 (MEN1). Men1(+/-) mice were treated from 12 months-of-age with 40 mg/kg pasireotide long-acting release (LAR) formulation, or phosphate-buffered saline (PBS), intramuscularly monthly for 9 months. The Men1(+/-) mice had magnetic resonance imaging at 12 and 21 months-of-age, and from 20 months-of-age oral 5-bromo-2-deoxyuridine for 1 month, to assess tumor development and proliferation, respectively. NETs were harvested at 21 months-of-age, and proliferation and apoptosis assessed by immunohistochemistry and TUNEL assays, respectively. Pasireotide-treated Men1(+/-) mice had increased survival (80.9 (pasireotide) vs. 65.2% (PBS), P<0.05), with fewer mice developing pancreatic NETs (86.9% (pasireotide) vs. 96.9% (PBS), P<0.05) and smaller increases in pituitary NET volumes (pre-treated vs. post-treated = 0.803 ±0.058mm(3) vs. 2.872 ±0.728 mm(3) (pasireotide) compared to 0.844 ±0.066mm(3) vs. 8.847 ±1.948mm(3) (PBS), P<0.01). In addition, pasireotide-treated mice had fewer pancreatic NETs compared to PBS-treated mice (2.36 ±0.25 vs. 3.72 ±0.32, respectively, P<0.001), with decreased proliferation in pancreatic NETs (0.35 ±0.03% (pasireotide) vs. 0.78 ±0.08% (PBS), P<0.0001) and pituitary NETs (0.73 ±0.07% (pasireotide) vs. 1.81 ±0.15% (PBS), P<0.0001), but increased apoptosis in pancreatic NETs (0.42 ±0.05% (pasireotide) vs. 0.19 ±0.03% (PBS), P<0.001) and pituitary NETs (14.75 ±1.58% (pasireotide) vs. 2.35 ±0.44% (PBS), P<0.001). Thus, pasireotide increased survival and inhibited pancreatic and pituitary NET growth, thereby indicating its potential as an anti-proliferative and pro-apoptotic therapy.

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