Abstract
Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 μg intraperitoneally or 5 μg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 μg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that MT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of MT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells. (C) 2000 Cancer Research Campaign.
| Original language | English |
|---|---|
| Pages (from-to) | 1724-1731 |
| Number of pages | 8 |
| Journal | British Journal of Cancer |
| Volume | 82 |
| Issue number | 10 |
| State | Published - May 10 2000 |
| Externally published | Yes |
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Keywords
- AgNOR
- Apoptosis
- Colon cancer
- GH-RH antagonists
- IGF-I
- IGF-I receptor
- IGF-II
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. / Szepeshazi, K.; Schally, Andrew V; Groot, K.; Armatis, P.; Halmos, G.; Hebert, F.; Szende, B.; Varga, J. L.; Zarandi, M.
In: British Journal of Cancer, Vol. 82, No. 10, 10.05.2000, p. 1724-1731.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers
AU - Szepeshazi, K.
AU - Schally, Andrew V
AU - Groot, K.
AU - Armatis, P.
AU - Halmos, G.
AU - Hebert, F.
AU - Szende, B.
AU - Varga, J. L.
AU - Zarandi, M.
PY - 2000/5/10
Y1 - 2000/5/10
N2 - Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 μg intraperitoneally or 5 μg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 μg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that MT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of MT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells. (C) 2000 Cancer Research Campaign.
AB - Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 μg intraperitoneally or 5 μg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 μg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that MT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of MT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells. (C) 2000 Cancer Research Campaign.
KW - AgNOR
KW - Apoptosis
KW - Colon cancer
KW - GH-RH antagonists
KW - IGF-I
KW - IGF-I receptor
KW - IGF-II
UR - http://www.scopus.com/inward/record.url?scp=0034110139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034110139&partnerID=8YFLogxK
M3 - Article
VL - 82
SP - 1724
EP - 1731
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 10
ER -