INHIBITION OF GROWTH OF HUMAN SMALL-CELL LUNG-CANCER BY BROMOCRIPTINE

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 D-2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D-2 receptor ligand, [I-125]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D-2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.