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 D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, 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.
Department of Medicine, Teikyo University School of Medicine, Kawasaki, Japan.
M
M
Ishibashi
M
M
Fujisawa
H
H
Furue
Y
Y
Maeda
M
M
Fukayama
T
T
Yamaji
D000818:Animals; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000737:chemistry / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000737:chemistry / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D011954:Receptors, Dopamine / Q000032:analysis; D014183:Transplantation, Heterologous; D014667:Vasopressins / Q000378:metabolism
D011954:Receptors, Dopamine; D014667:Vasopressins; D001971:Bromocriptine