Growth hormone receptor antagonist administration inhibits growth of human colorectal carcinoma in nude mice.
Increasing evidence has accumulated in support of the hypothesis that growth hormone (GH) and insulin-like growth factors (IGFs) play a role in carcinogenesis. In order to test this hypothesis, female nude mice were xenografted with two different human colorectal cancer cell lines (COLO 205 and HT-29) and randomized to receive placebo or a GH receptor antagonist (GHRA) (B2036-PEG) every second day for 16 days. The tumour volume was measured in each animal throughout the study and by the end of the experiment the tumour weights were recorded. After 16 days of therapy in nude mice with the COLO 205 colorectal cancer, GHRA treatment caused a 39% reduction in tumour volume (p < 0.02) and a 44% reduction in tumour weight (p < 0.01). GHRA treatment equally reduced circulating IGF-I and IGFBP-3 levels, while apoptosis was increased in the treatment group. Expression of IGF-I, IGF-II and the corresponding receptors in COLO 205 tumours was also decreased by the treatment. GHRA had no effect on the growth of the HT-29 colorectal cancer despite pronounced reduction in serum IGF-I. The present study thereby demonstrates a central role for the GH/IGF system in the pathogenesis of some colorectal cancers and suggests that specific GHR blockade may present a new concept in the treatment of colorectal cancer.
Dagnaes-Hansen
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F
Department of Medical Microbiology and Immunology, Bartholin Building, Wilhelm Meyers Alle 240, University of Aarhus, DK-8000 Aarhus C, Denmark. mikrfdh@medmicro.au.dk
Duan
H
H
Rasmussen
L M
LM
Friend
K E
KE
Flyvbjerg
A
A
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000097:blood; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D019073:HT29 Cells; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C406545:pegvisomant; C051815:somatotropin-binding protein