EFFECT OF HUMAN GROWTH-HORMONE ON HUMAN PANCREATIC-CARCINOMA GROWTH, PROTEIN, AND CELL-CYCLE KINETICS

The role of human growth hormone (hGH) as a nutritional adjunct for ca ncer patients is controversial because of its potential mitogenic effe cts on tumor growth. No studies to date have examined the effect of hG H on human tumor response in vivo. In Vitro: Athymic mice were injecte d (s.c.) daily with hGH (GH, n = 14) or saline (CTL, n = 14). On Day 1 0, serum was collected and added to human pancreatic carcinoma cells i n culture. In Vivo: Athymic mice were inoculated (s.c.) with human pan creatic carcinoma cells. On Day 14, mice were randomized to receive da ily either hGH (GH, n = 14) or saline (CTL, n = 12). On Day 29, animal s received [H-3]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics an alyzed. Data are expressed as mean +/- SEM. Statistical analysis was p erformed by unpaired t test 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 x 10(8)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P < 0.001). In Vivo: Serum from GH-treated animals had el evated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P < 0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) comp ared with CTL serum (925 +/- 31 vs 747 +/- 38, P < 0.001). In Vivo: Gr owth hormone had no significant effect on tumor growth rate (mm(3)/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 h ormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 C TL vs 222 +/- 53 GH, P < 0.005) and liver FSR (%/day) (62.8 +/- 17.8 C TL vs 79.7 +/- 12.7 GH, P < 0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo GH administration rais ed serum IGF-1 levels and increased liver protein FSR, without tumor g rowth, cell cycle kinetics, or protein FSR. (C) 1996 Academic Press, I nc.