SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells

Terry W. Moody, Jessica Chiles, Marchessini Casibang, Elizabeth Moody, Daniel Chan, Thomas P Davis

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. 3H-SR48692 bound with high affinity (IC50 = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific 125I-NT binding with high affinity (IC50 values of 2 and 200 nM). In contrast, the NT2 receptor agonist, levocabastine, had little effect on specific 125I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 μM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 μM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT1 receptor antagonist which inhibits SCLC growth.

Original languageEnglish (US)
Pages (from-to)109-115
Number of pages7
JournalPeptides
Volume22
Issue number1
DOIs
Publication statusPublished - 2001

    Fingerprint

Keywords

  • C-fos mRNA
  • Cytosolic Ca
  • Lung cancer
  • Proliferation
  • Receptor binding
  • SR48692

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this