J. Pinski et al., INHIBITION OF GROWTH OF HUMAN SMALL-CELL AND NONSMALL CELL LUNG CARCINOMAS BY ANTAGONISTS OF GROWTH HORMONE-RELEASING HORMONE (GH-RH), International journal of oncology, 9(6), 1996, pp. 1099-1105
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.