Abstract
Small cell lung carcinoma (SCLC) is a common and frequently fatal malignancy for which there is no satisfactory treatment. The amphibian peptide bombesin and its mammalian counterpart, gastrinreleasing peptide, act as autocrine growth factors for SCLC cells. Vasoactive intestinal peptide (VIP) inhibited the growth and multiplication of a SCLC cell line, NCl-H345. VIP-induced suppression of cell proliferation was enhanced by an anti-bombesin monoclonal antibody. Isobutylmethyl xanthine (IBMX) and forskolin, which elevate intracellular cyclic (c) AMP levels, enhanced VIP-stimulated cAMP production. IBMX and forskolin inhibited cell growth and enhanced VIP-induced suppression of cell proliferation. The inhibition by VIP and other cAMP-promoting agents paralleled their ability to stimulate cellular production of cyclic adenosine monophosphate. The anti-mitogenic activity of VIP and its enhancement by anti-bombesin antibody and other cAMP-promoting agents provide a potential new approach to the treatment of SCLC.