INHIBITION OF GROWTH OF HUMAN SMALL-CELL AND NONSMALL CELL LUNG CARCINOMAS BY ANTAGONISTS OF GROWTH HORMONE-RELEASING HORMONE (GH-RH)

Insulin-like growth factors-I and-II (IGF-I and IGF-II) may be involve d in the proliferation of human lung carcinomas. The purpose of this s tudy was to investigate the effects of two potent antagonists of growt h hormone-releasing hormone (GH-RH), MZ-4-71 and MZ-5-156 on the growt h of the H69 human small cell lung cancer (SCLC) and H157 non-SCLC (NS CLC) 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 o r MZ-5-156 injected s.c. twice a day at a dose of 20 mu g/animal. Grow th 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 weigh t. 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 w ith MZ-4-71 were decreased. High affinity binding sites for ICF-I were demonstrated on membranes of H69 and H157 tumors. In cell cultures, t he 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 antago nist. Our findings demonstrate that the GHRH antagonists MZ-4-71 and M Z-5-156 can inhibit the growth of SCLC and NSCLC. This new approach to the management of lung cancer merits further investigation.