Inhibition of growth of human small cell and non-small cell lung carcinomas by antagonists of growth hormone-releasing hormone (GH-RH)

Jacek Pinski, Andrew V. Schally, Andreas Jungwirth, Kate Groot, Gabor Halmos, Patricia Armatis, Marta Zarandi, Manuel Vadillo-Buenfil

Research output: Contribution to journalArticle

51 Scopus citations

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 μg/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 IGF-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 GH-RH 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.

Original languageEnglish (US)
Pages (from-to)1099-1105
Number of pages7
JournalInternational journal of oncology
Volume9
Issue number6
DOIs
StatePublished - Dec 1996

Keywords

  • GH-RH antagonists
  • IGF-I
  • IGF-II
  • lung cancer
  • non-SCLC
  • SCLC

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Inhibition of growth of human small cell and non-small cell lung carcinomas by antagonists of growth hormone-releasing hormone (GH-RH)'. Together they form a unique fingerprint.

  • Cite this