Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix inhibits growth of DU-145 human androgen-independent prostate carcinoma in nude mice and suppresses the levels and mRNA expression of IGF-II in tumors

In previous studies, we showed that LH-RH antagonist Cetrorelix inhibits the growth of DU-145 and PC-3 human androgen-independent prostate cancers in nude mice. To investigate the mechanisms involved, we treated male nude mice bearing xenografts of DU-145 human androgen-independent prostate cancer with Cetrorelix at a dose of 100 mu g/animal subcutaneously (s.c.) once a day. Tumor growth, serum and tumor levels of IGF-I and -II as well as the mRNA expression of IGF-I and -II in tumors were evaluated. After 8 weeks of treatment, final volume and weight of DU-145 tumors in mice treated with Cetrorelix were significantly decreased compared with controls and serum IGF-1 showed a significant reduction. Therapy with Cetrorelix also reduced by 84% the levels of IGF-II in DU-145 tumor tissue compared with controls, but did not affect the concentration of IGF-I. RT-PCR analyses revealed a high expression of mRNA for IGF-II, but not for IGF-I in DU-145 tumors. Treatment with Cetrorelix decreased the expression of IGF-II mRNA by 78% (p < 0.01) as compared with controls. Our study indicates that LH-RH antagonist Cetrorelix may inhibit the growth of DU-145 human androgen-independent prostate cancers by decreasing the production and mRNA expression of IGF-II by the tumor tissue. This also suggests that LH-RH antagonist Cetrorelix could interfere with the signal transduction pathways involving IGF-II, leading to tumor growth inhibition. (C) 1998 Elsevier Science BN. All rights reserved.