Effect of Human Growth Hormone on Human Pancreatic Carcinoma Growth, Protein, and Cell Cycle Kinetics

Abstract

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor responsein vivo. In Vitro:Athymic mice were injected (s.c.) daily with hGH (GH,n= 14) or saline (CTL,n= 14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture.In Vivo:Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH,n= 14) or saline (CTL,n= 12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean ± SEM. Statistical analysis was performed by unpairedttest and/or ANOVA where appropriate.In Vitro:Serum from GH-treated animals had elevated IGF-1 levels (287 ± 34 ng/ml vs 157 ± 53 ng/ml,P< 0.001) and significantly stimulated cell growth (No. cells × 103/well) compared with CTL serum (925 ± 31 vs 747 ± 38,P< 0.001).In Vivo:Serum from GH-treated animals had elevated IGF-1 levels (287 ± 34 ng/ml vs 157 ± 53 ng/ml,P< 0.001) and significantly stimulated cell growth (No. cells × 103/well) compared with CTL serum (925 ± 31 vs 747 ± 38,P< 0.001).In Vivo:Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 ± 0.47 CTL vs 1.57 ± 0.66 GH), final tumor weight (mg) (0.19 ± 0.15 CTL vs 0.17 ± 0.06 GH), DNA Index (1.5 ± 0.1 CTL vs 1.5 ± 0.1 GH), percent S phase (20.3 ± 3.3 CTL vs 22.1 ± 3.0 GH), or tumor FSR (%/day) (51.1 ± 17.8 CTL vs 70.2 ± 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 ± 48 CTL vs 222 ± 53 GH,P< 0.005) and liver FSR (%/day) (62.8 ± 17.8 CTL vs 79.7 ± 12.7 GH,P< 0.005). Serum of GH-treated mice increased human pancreatic cell growthin vitro. In vivo,GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR.