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.