Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo
- Department of Medicine, Northport Veterans Affairs Medical Center Stony Brook, NY 11768-2290, and State University of New York, Health Sciences Center 17-040, Stony Brook, NY 11794-8172
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Communicated by Susan E. Leeman, Boston University School of Medicine, Boston, MA (received for review March 15, 1998)
Abstract
Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal 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 apparently 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 intracellular cAMP levels, and the inhibition was abolished by selective inhibition of cAMP-dependent protein kinase. If confirmed in clinical trials, this antiproliferative action of vasoactive intestinal peptide may offer a new and promising means of suppressing SCLC in human subjects, without the toxic side effects of chemotherapeutic agents.
Footnotes
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↵ * Present address: Department of Surgery, Teikyo University Hospital, 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki, Kanagawa 213-8507, Japan.
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↵ † Present address: Department of Surgery, University of Michigan, Ann Arbor, MI 48109-0329.
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↵ ‡ To whom reprint requests should be addressed. e-mail: ssaid{at}mail.som.sunysb.edu.
- ABBREVIATIONS:
- protein kinase A,
- cAMP-dependent protein kinase;
- DMSO,
- dimethyl sulfoxide;
- IBMX,
- 3-isobutyl-1-methylxanthine;
- NCI,
- designator of cell lines developed by the National Cancer Institute;
- SCLC,
- small-cell lung cancer;
- VIP,
- vasoactive intestinal peptide
- Copyright © 1998, The National Academy of Sciences
