VASOACTIVE-INTESTINAL-PEPTIDE INHIBITS HUMAN SMALL-CELL LUNG-CANCER PROLIFERATION IN-VITRO AND IN-VIVO

Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive i ntestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparent ly by a cAMP-dependent mechanism, because the inhibition was enhanced by the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine in proportion to increases in i ntracellular cAMP levels, and the inhibition was abolished by selectiv e inhibition of cAMP-dependent protein kinase. If confirmed in clinica l trials, this antiproliferative action of vasoactive intestinal pepti de may offer a new and promising means of suppressing SCLC in human su bjects, without the toxic side effects of chemotherapeutic agents.