A novel bombesin receptor antagonist inhibits autocrine signals in a small cell lung carcinoma cell line

Abstract

The human small cell lung carcinoma (SCLC) cell line NCI-H345 constitutively produces gastrin-releasing peptide (GRP), a peptide homologous to the mitogen bombesin. In addition, NCI-H345 cells express bombesin receptors and respond to bombesin with rapid activation of phospholipase C and mobilization of intracellular Ca2+. Treatment of NCI-H345 cells with a novel potent bombesin receptor antagonist [Leu13-psi-CH2NH-Leu14]bombesin blocked the increase in phosphatidylinositol turnover and cytoplasmic free Ca2+ ([Ca2+]i) stimulated by bombesin. Furthermore [Leu13-psi-CH2NH-Leu14]bombesin inhibited NCI-H345 colony formation in defined semisolid medium in the absence of exogenous GRP. The rapid, hormone-induced accumulation of inositol(1,4,5)trisphosphate was markedly more sensitive to antagonist inhibition than the hormone-induced Ca2+ transient, the sustained accumulation of inositol monophosphates, or colony formation in soft agarose. These data demonstrated inhibition of transmembrane signals associated with autocrine growth control in SCLC by a novel peptide receptor antagonist.