Endocrine Abstracts (2011) 26 P74

In vitro effect of the somatostatin analogue BIM 23704 on cell cycle timecourse in an ovarian carcinoma cell line

Cristina de Angelis1, Claudia Pivonello1, Gaia Cuomo1, Attilio di Spiezio Sardo2, Guiseppe Bifulco2, Carmine Nappi2, Francesco Sabbatino1, Federica Cariati1, Annamaria Colao1 & Rosario Pivonello1

1Department of Endocrinology and Clinical and Molecular Oncology, University of Naples Federico II, Naples, Italy; 2Department of Gynecology and Obstetrics, University of Naples Federico II, Naples, Italy.

Ovarian carcinoma (OC) is associated with poor prognosis and low survival rate. Eligible treatment for advanced OC is surgery followed by chemotherapy based on a combination of Platinum and Taxol, but unfortunately long-term outcome of such therapy is disappointing. Moreover, systemic administration of cytotoxic agents is usually accompanied by a series of side effects. On the basis of this evidence, more selective and tumour cell-targeted therapeutic approaches are warranted. Somatostatin receptors (SSTRs) are widely distributed in normal and tumour tissues and mediate anti-proliferative, anti-angiogenic and pro-apoptotic effects acting on different molecular pathways. The aim of this study was to analyze SSTRs expression in A2780 human ovarian adenocarcinoma cell line and tested the effect of a SSTR selective agonist on cell line proliferation. PCR analysis showed SSTR1 and SSTR2 expression, suggesting to test the effect of the SSTR agonist BIM 23704, which has high affinity for these two receptors. BIM 23704, administered at the dose of 10−7 –10−9 M, showed a dose-dependent inhibitory effect on cell proliferation with a maximum effect after 48 h of continuous exposure (30% at 10−7 M and 25% at 10−9 M). This effect persist until 96 h of exposure, then treated cells become insensitive. FACS analysis indicated that this inhibitory effect is not due to induction of apoptosis nor to block of cell cycle but to a slowdown of cell cycle timecourse (reduction of 11%). Western blot analysis showed a reduction of pERK1/2(Tyr 204) kinases in treated cells protein extracts compared with untreated control cells suggesting an involvement of these proteins in A2780 cell cycle. These preliminary data, if confirmed, might suggest the use of this compound as adjuvant of chemotherapeutic agents in the effort to reduce their dose and consequent side effects and to bypass the onset of chemoresistance due to high dosage and continuous exposure in the management of OC.