title: Inhibition of growth of human small cell and non-small cell lung carcinomas by antagonists of growth hormone-releasing hormone (GH-RH).
abstract: Insulin-like growth factors-I and-II (IGF-I and IGF-II) may be involved in the proliferation of human lung carcinomas. The purpose of this study was to investigate the effects of two potent antagonists of growth hormone-releasing hormone (GH-RH), MZ-4-71 and MZ-5-156 on the growth of the H69 human small cell lung cancer (SCLC) and H157 non-SCLC (NSCLC) lines transplanted into nude mice or cultured in vitro. Nude mice bearing H69 and H157 tumors were treated for 3-5 weeks with MZ-4-71 or MZ-5-156 injected s.c. twice a day at a dose of 20 mu g/animal. Growth of H69 and H157 tumors in nude mice was significantly inhibited by MZ-4-71 and MZ-5-156 as shown by a reduction in tumor volume and weight. In animals bearing H157 NSCLC, treatment with MZ-4-71 decreased IGF-I and IGF-II levels in tumor tissue. Levels of IGF-I, but not of IGF-II in serum and liver tissue of H157 tumor-bearing nude mice treated with MZ-4-71 were decreased. High affinity binding sites for ICF-I were demonstrated on membranes of H69 and H157 tumors. In cell cultures, the proliferation rate of H69 SCLC cells was suppressed by 10(-7)-10(-5) M MZ-4-71, but H157 NSCLC line was only inhibited by 10(-5) M antagonist. Our findings demonstrate that the GHRH antagonists MZ-4-71 and MZ-5-156 can inhibit the growth of SCLC and NSCLC. This new approach to the management of lung cancer merits further investigation.
authors.affiliation: VET AFFAIRS MED CTR,INST ENDOCRINE POLYPEPTIDE & CANC,NEW ORLEANS,LA 70146. TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70146.
authors.forename: J
authors.initials: J
authors.lastname: Pinski
authors.forename: A
authors.initials: A
authors.lastname: Schally
authors.forename: A
authors.initials: A
authors.lastname: Jungwirth
authors.forename: K
authors.initials: K
authors.lastname: Groot
authors.forename: G
authors.initials: G
authors.lastname: Halmos
authors.forename: P
authors.initials: P
authors.lastname: Armatis
authors.forename: M
authors.initials: M
authors.lastname: Zarandi
authors.forename: M
authors.initials: M
authors.lastname: Vadillobuenfil