Somatostatin (SRIF) analogs have been employed in medical
therapy of non-functioning
pituitary adenomas (NFA), with contrasting results. Previous evidence showed that SRIF can exert its antiproliferative effects by reducing
vascular endothelial growth factor (
VEGF) secretion and action, and that
VEGF expression may be related to
pituitary tumor growth. The aim of our study was to clarify the possible effects of a multireceptor SRIF
ligand on
VEGF secretion and cell proliferation in human NFA primary cultures. We assessed the expression of SRIF receptors (SSTR1-5), the in vitro effects on
VEGF secretion, and on cell viability of SRIF and of the stable SRIF analog
pasireotide (
SOM230), which activates
SSTR1, 2, 3, and 5. Twenty-five NFA were examined by RT-PCR for expression of alpha-subunit, SSTR,
VEGF, and
VEGF receptors 1 (VEGF-R1) and 2 (VEGF-R2). Primary cultures were tested with SRIF and with
pasireotide. All NFA samples expressed alpha-sub,
VEGF and
VEGFR-1 and 2, while SSTR expression pattern was highly variable. Two different groups were identified according to
VEGF secretion inhibition by SRIF.
VEGF secretion and cell viability were reduced by SRIF and
pasireotide in the 'responder' group, but not in the 'non-responder' group, including NFA expressing SSTR5. SRIF and
pasireotide completely blocked
forskolin-induced
VEGF secretion. In addition, SRIF and
pasireotide completely abrogated the promoting effects of
VEGF on NFA cell viability. Our data demonstrate that
pasireotide can inhibit NFA cell viability by inhibiting
VEGF secretion, and suggest that the multireceptor-SSTR agonist
pasireotide might be useful in medical
therapy of selected NFA.