Effects of plasmid-mediated growth hormone-releasing hormone supplementation on LL-2 adenocarcinoma in mice.
This study was designed to measure the effects of plasmid growth hormone-releasing hormone (GHRH) supplementation on LL-2 (Lewis lung adenocarcinoma) tumor-bearing immunocompetent mice. Male and female mice (n = 20/group/experiment) received 2.5 x 10(6) LL-2 cells in the left flank. One day later, we injected the mice intramuscularly with 20 micro g of a myogenic plasmid, pSP-hGHRH or pSP-betagal, as a control. Mean serum IGF-I was significantly higher in treated animals versus controls (P < 0.05). Male and female mice constitutively expressing GHRH exhibited a decline in tumor growth rate relative to controls (20% for males, P < 0.03, and 11% for females, P < 0.13). Histopathological analysis revealed that treated animals were less likely to develop lung metastases than controls (11%) and had no alternate-organ metastases. The number of metastases/lung was reduced by 57% in female mice with GHRH treatment (P < 0.006). When tumor size exceeded 8% of body weight, GHRH-treated mice showed normal urea, creatinine, and kidney volume, while controls displayed signs of renal insufficiency. This study provides evidence that with plasmid-mediated GHRH supplementation in tumor-bearing mice, tumor growth rate is not increased but is actually attenuated.
Khan
Amir S
AS
ADViSYS, Inc., The Woodlands, Texas 77381, USA.
Anscombe
Ingrid W
IW
Cummings
Kathleen K
KK
Pope
Melissa A
MA
Smith
Louis C
LC
Draghia-Akli
Ruxandra
R
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D008297:Male; D051379:Mice; D010957:Plasmids; D051381:Rats; D013997:Time Factors
D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone