UKINETS2024 22nd Annual Meeting of the UK and Ireland Neuroendocrine Tumour Society 2024 Poster Presentations (33 abstracts)
1Centre for Health and Life Sciences, Coventry University, Coventry, United Kingdom. 2Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospital of Coventry and Warwickshire, Coventry, United Kingdom. 3Institute of Cardio-Metabolic Medicine, University Hospital of Coventry and Warwickshire, Coventry, United Kingdom. 4Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom. 5Abcam PLC, Oxford, United Kingdom
Introduction: Neuroendocrine neoplasms (NENs) represent a diverse group of tumours with varying clinical presentations and outcomes. Despite advancements in treatment, there remains a need to better understand the behaviour of somatostatin receptors (SSTRs) to monitor disease progression and therapeutic efficacy. Our study aims to evaluate the impact of octreotide acetate (OA), Lanreotide acetate (LA) and Pasireotide (P) on LCC-18 cells, investigating potential mechanisms behind the eventual loss of drug efficacy. Specifically, we focus on the changes in SSTRs 2, 3, 4 and 5, as well as the proliferation marker Ki-67 following drug exposure.
Materials and Methods: The LCC-18 cell line, grade 3 NEN from a colonic tumour, was cultured and treated for 2 hours with increasing concentrations of OA, LA and P (6.25 µM to 100 µM). Immunocytochemistry (ICC) and qRT-PCR was used to determine expression SSTRs 2, 3, 4 and 5 and Ki-67 following acute exposure to the respective SSTR analogues and 2 hours. Additionally, apoptosis induction was assessed for each drug to explore their potential cytotoxic effects.
Results: Preliminary results showed no evidence of apoptosis following exposure to either OA or LA; in contrast, P demonstrated a faint level of apoptosis, with a small percentage of cells undergoing apoptosis at 100 µM. The ICC and qRT-PCR data, which further reveal the impact of these drugs on SSTRs and Ki-67 expression, are still in progress and will provide valuable insights upon completion.
Conclusion: By focusing on early changes post-drug exposure, we aim to identify potential biomarkers that could predict therapeutic efficacy and guide clinical decision-making by elucidating the changes in SSTRs and Ki-67 expression. This research aims to improve future treatment strategies and more personalised approaches for patients with NENs, ultimately enhancing therapeutic outcomes by identifying early biomarkers of drug efficacy.