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Inhibition of Growth of Human Small Cell Lung Cancer by Bromocriptine

Fourth Department of Medicine, Teikyo University School of Medicine, Kawasaki, [M. I., H. F.], and Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo [M. F., T. Y.], and Department of Pathology, Tokyo Metropolitan Komagome Hospital, Tokyo, [Y. M., M. F.] Japan

Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D₂ receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D₂ receptor ligand, [¹²⁵I]idosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D₂ receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.

¹ To whom requests for reprints should be addressed, at Fourth Department of Medicine, Teikyo University School of Medicine, 74 Mizohokuchi, Takatsu-Ku, Kawasaki, Kanagawa 213, Japan.

Received 1/18/94. Accepted 5/ 4/94.

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