title: Inhibition of human non-small cell lung cancers with a targeted cytotoxic somatostatin analog, AN-162.
abstract: 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 microM concentrations) and in vivo on H460 and H1299 NSCLCs xenografted into nude mice (at the dose of 2.5 micromol/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-162 significantly decreased cell proliferation in vitro and tumor growth (p<0.05 vs. all groups) of H460 and H1299 NSCLCs in vivo. Based on real-time PCR array data, AN-162 induced several apoptosis-related genes in vivo in both models. Our results suggest that cytotoxic somatostatin analog AN-162 (AEZS-124) should be considered for the further development of a therapy of patients with NSCLC.
authors.affiliation: Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, 1201 NW 16th Street,Miami, FL 33125, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Treszl
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Stephan
authors.initials: S
authors.lastname: Seitz
authors.forename: Luca
authors.initials: L
authors.lastname: Szalontay
authors.forename: Ferenc G
authors.initials: FG
authors.lastname: Rick
authors.forename: Karoly
authors.initials: K
authors.lastname: Szepeshazi
authors.forename: Gabor
authors.initials: G
authors.lastname: Halmos
mesh_terms: D015078:2-Hydroxyphenethylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001667:Binding, Competitive; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry; D011986:Receptors, Somatotropin / Q000235:genetics; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry; D015854:Up-Regulation / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004337:Drug Carriers; D011986:Receptors, Somatotropin; C000956:N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline; D013004:Somatostatin; D015078:2-Hydroxyphenethylamine; D004317:Doxorubicin; C053408:RC 121; D015282:Octreotide