Inhibition of human non-small cell lung cancers with a targeted cytotoxic somatostatin analog, AN-162

Human non-small cell lung cancers (NSCLCs) express receptors for somatostatin. The cytotoxic analog of somatostatin AN-162 (AEZS-124), consisting of doxorubicin linked to a somatostatin analog RC-121 binds to receptors for somatostatin and is targeted to tumors expressing these receptors. The aim of this study was to investigate the effect of targeted cytotoxic somatostatin analog AN-162 on a panel of human NSCLC cell lines (A549, H460, H838, H1299) in vitro (at 0.5-100 mu M concentrations) and in vivo on H460 and H1299 NSCLCs xenografted into nude mice (at the dose of 2.5 mu mol/kg, i.v., once a week). The expression of mRNA for somatostatin receptor subtypes was investigated by RT-PCR in cell lines and tumor tissues. Somatostatin receptor proteins were also characterized by ligand competition assay and Western blotting. AN-I 62 significantly decreased cell proliferation in vitro and tumor growth (p < 0.05 vs. all groups) of H460 and HI 299 NSCLCs in vivo. Based on real-time PCR array data, AN-I 62 induced several apoptosis-related genes in vivo in both models. Our results suggest that cytotoxic somatostatin analog AN-I 62 (AEZS-124) should be considered for the further development of a therapy of patients with NSCLC. (C) 2009 Elsevier Inc. All rights reserved.