Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160 inhibit the growth of the OV-1063 human epithelial ovarian cancer cellline xenografted into nude mice

The effects of antagonists of GHRH and the somatostatin analog RC-160 on th e growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 mug/day of the GHRH antagoni st JV-1-36 or MZ-5-156 and 60 mug/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9% (P < 0.01), 58.3% (P < 0.05), and 60.6% (P < 0.01), respectively, us, the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 signific antly reduced serum insulin-like growth factor I (IGF-I). The levels of mes senger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRN A for IGF I was detected, but treatment with JV-1-136 caused a 51.8% decrea se (P < 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-106 3 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P < 0.05 ) stimulated cell growth, but 10(-5) mol/L JV-1-36 nearly completely inhibi ted (P < 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA f or GHRH receptors and showed the presence of binding sites for GHRH. Our re sults indicate that antagonistic analogs of GHRH and the somatostatin analo g RC-160 inhibit the growth of epithelial ovarian cancers. The effects of R C-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, where as GHRH antagonists appear to reduce IGF-II production and interfere with t he autocrine regulatory pathway. The antitumorigenic action of GHRH antagon ists appears to be mediated by GHRH receptors found in OV-1063 tumors.