Abstract
PURPOSE: To evaluate the tumor inhibitory activities of antagonists of growth hormone-releasing hormone (GH-RH) and vasoactive intestinal peptide (VIP) in UCI-107 human ovarian cancer model, and to investigate the role of the insulin-like growth factor (IGF) system in the response. METHODS: In the present study we investigated the effects of GH-RH antagonist JV-1-36 and VIP antagonist JV-1-52, on the growth and tumorigenicity of UCI-107 ovarian cell carcinoma xenografted into nude mice. Studies on the effects of hGH-RH(1-29)NH2, IGF-I, IGF-II, JV-1-36, and JV-1-52 on the proliferation of UCI-107 cells cultured in vitro were also performed. RESULTS: After 22 days of therapy with JV-1-36 or JV-1-52 at the dose of 20 microg/day, the final volume of UCI-107 tumors was significantly (P<0.05) decreased by 50.5% and 56%, respectively, compared to controls. The concentration of IGF-II in tumors was reduced by 66% in the JV-1-36-treated group and by 62% in the group given JV-1-52 (both P < 0.05). Exposure in vitro to 1 microM concentrations of JV-1-36 or JV-1-52 for 24 h decreased the tumorigenicity of UCI-107 cells in nude mice. All ten mice injected with cells treated with medium alone developed tumors within 23 days after cell inoculation, while only eight of ten and four of ten mice injected with cells exposed to JV-1-36 or JV-1-52, respectively, had tumors. In vitro exposure of UCI-107 cells to 5-35 ng/ml IGF-II produced a significant suppression in the rate of cell proliferation (P < 0.01). CONCLUSION: Our results suggest that GH-RH and VIP antagonists inhibit the growth of UCI-107 ovarian cell carcinoma by mechanisms that appear to involve direct effects on the cancer cells.