Endocrine Abstracts (2006) 11 P551

In vitro effects of som230 on primary cultured pheochromocytoma cells

D Pasquali, G Conzo, V Rossi, G Bellastella, L Maione, A Bellastella & AA Sinisi

Second University of Naples, Internistica Clinica e Sperimentale, Sezione di Endocrinologia, Napoli, Italy.

The stable somatostatin analog octreotide has been successfully used for imaging and treatment of a variety of human tumors. Octreotide treatment has been reported of limited value in pheochromocytoma (PHEO). PHEOs often express more than one somatostatin receptor, and it is uncertain by which receptor subtype the functional responses of octreotide are mediated. A recent study showed by immunohistochemical staining that vast majority of tumors (90%) were positive for sst(3), immunoreactive sst(2A) receptors were only seen in 13 tumors (25%). All other somatostatin receptor subtypes were less frequently detected. These data suggest that these tumors may represent a potential target treatment with somatostatin receptor agonists with improved sst(3) activity. Octreotide is able to bound with high affinity SSTR2 e 5 while SOM230, a new synthetic analogue is active on SSTR1, 2, 3, 5. In this study we investigated the effects of the new synthetic SST analogue SOM230 on the control of growth and apoptosis in primary PHEO cell cultures obtained from a patient underwent to adrenalectomy.

Methods: Primary culture of cells were cultured in HAM F 12/dMEM, with 10% FCS. The cells (Pheo-c) characterized by immunohistochemistry were positive for chromogranin and NSE. Pheo-c were starved without FCS for 2 days, then treated with 10 nM, 100 nM SOM230 and octreotide for 48 h. For the analysis of proliferation and apoptosis, cells were harvested after treatment, and analyzed by MTT and TUNEL techniques.

Results: Pheo-c, after 48 h treatment with 100 nM OCT or SOM230, showed a significant cell growth reduction (P<0.05 and P<0.001 respectively) and this effect increased after 72 h. Induction of apoptosis was detected after 72 h of 100 nM OCT (8%) or SOM230 (16%) exposure of cells.

Conclusions: Our data suggest that SOM230 could be usefull to improve diagnostic imaging evaluation, and fpr the long-term treatment of patients with malignant or recurrent PHEO

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