Growth hormone releasing hormone plasmid supplementation, a potential treatment for cancer cachexia, does not increase tumor growth in nude mice.
Growth hormone releasing hormone (GHRH) is known to have multiple anabolic effects and immune-stimulatory effects. Previous studies suggest that treatment with anabolic hormones also has the potential to mitigate the deleterious effects of cancer cachexia in animals. We studied the effects of plasmid-mediated GHRH supplementation on tumor growth and the role of antitumor immune cells with two different human tumor cell lines, NCI-H358 human bronchioalveolar carcinoma and MDA-MB-468 human breast adenocarcinoma, subcutaneously implanted in nude mice. GHRH supplementation by delivery of human GHRH from a muscle-specific GHRH expression plasmid did not increase tumor progression in tumor-bearing nude mice. Male animals implanted with the NCI-H358 tumor cell line and treated with the GHRH-expressing plasmid exhibited a 40% decrease in the size of the tumors (P<.02), a 48% increase in white blood cells (P<.025) and a 300% increase in monocyte count (P<.0001), as well as an increase in the frequency of activated CD3+ and CD4+ cells in the tumors, compared to tumors of control animals. No adverse effects were observed in animals that received the GHRH-plasmid treatment. The present study shows that physiological stimulation of the GHRH-GH-IGF-I axis in mice with cancer does not promote tumor growth and may provide a viable treatment for cancer cachexia in humans.
Khan
Amir S
AS
ADViSYS, Inc., The Woodlands, Texas 77381, USA.
Smith
Louis C
LC
Anscombe
Ingrid W
IW
Cummings
Kathleen K
KK
Pope
Melissa A
MA
Draghia-Akli
Ruxandra
R
D000230:Adenocarcinoma / Q000150:complications / Q000473:pathology*; D000818:Animals; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology*; D017252:CD3 Complex; D015704:CD4 Antigens; D002100:Cachexia / Q000628:therapy* / Q000662:veterinary; D018450:Disease Progression; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics* / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes; D010957:Plasmids / Q000235:genetics; D014183:Transplantation, Heterologous
D017252:CD3 Complex; D015704:CD4 Antigens; D013007:Growth Hormone-Releasing Hormone