Endocrine Abstracts

Introduction: Neuroendocrine neoplasms (NENs) represent a heterogeneous group of tumours with variable clinical behaviour and prognosis. Somatostatin analogues (SSAs) are central to NEN management through modulation of somatostatin receptors (SSTRs), yet the molecular mechanisms underlying receptor regulation and therapeutic resistance remain poorly defined. This study investigated the effects of octreotide acetate (OA), lanreotide acetate (LA), and pasireotide (P) on the expression of SSTR subtypes 2, 3, 4 and 5, and the proliferation marker Ki-67, in LCC-18 neuroendocrine tumour cells.

Material and Methods: LCC-18 cells, derived from grade 3 NEN, were exposed to increasing concentrations (6.25-100 µM) of OA, LA and P for 2 hours. Expression of SSTR subtypes and Ki-67 was evaluated using immunocytochemistry (ICC) and quantitative real-time PCR (qRT-PCR). Apoptosis was assessed using an Annexin V assay to determine potential cytotoxic effects.

Results: Preliminary findings revealed no significant apoptotic induction with OA or LA treatment, whereas P elicited a mild apoptotic response at 100 µM (P = 0.032). The qRT-PCR analysis showed distinct, dose-dependent modulation of SSTR expression: OA and LA upregulated SSTR2 and SSTR5 at moderate concentrations, while P induced broader activation of SSTR3 and SSTR4 accompanied by reduced Ki-67 expression, suggesting an antiproliferative effect. These results indicate that each analogue exerts a unique receptor-specific regulatory profile that may influence treatment responsiveness and receptor internalisation dynamics.

Conclusion: Each molecular profiling of SSTR and Ki-67 expression following SSA exposure may help identify biomarkers predictive of therapeutic efficacy. Understanding these regulatory mechanisms could guide more personalised therapeutic strategies and improve clinical outcomes for patients with NENs.