Induction of Apoptosis in Neuroendocrine Tumors of the Digestive System During Treatment with Somatostatin Analogs

Abstract

The extent of apoptosis identified by in situ DNA nick end labelling (TUNEL) on tissue samples obtained from patients with neuroendocrine tumors was correlated with the clinical outcome in patients treated with high-dose somatostatin analog (lanreotide 12 mg/day), n = 8, or other biotherapy including interferon-alpha (IFN-α), n = 4, low-dose somatostatin analog (octreotide or lanreotide), n = 3, or a combination of both, n = 1. Biopsies were obtained before the start of treatment and/or after 6 months and 12 months. After 6 months of treatment, 5 patients receiving high-dose somatostatin analog showed a biochemical response (decrease in different neuroendocrine tumor markers) and 4 of these showed an increase in apoptotic index (AI: percentage of apoptotic cells) by 1.94 ± 1.71%. At 12 months, AI was also increased in patients with a biochemical response (4.22 ± 3.93%). However, none showed a decrease in tumor size on computerized tomography (CT) and none of the patients treated with low-dose somatostatin analog or IFN-α showed any significant increase in AI during treatment. In an experimental model, nude mice were xenografted with the neuroendocrine cell line (BON-I)