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.

Abstract

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 microg/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.

• Authors: N Lamharzi, A V Schally, M Koppán
• Journal: Regulatory peptides (Regul Pept) Vol. 77 Issue 1-3 Pg. 185-92 (Oct 16 1998) ISSN: 0167-0115 [Print] Netherlands
• PMID: 9809814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Androgens
• Antineoplastic Agents
• Hormone Antagonists
• RNA, Messenger
• Gonadotropin-Releasing Hormone
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II
• cetrorelix

Topics

• Androgens (metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Cell Division (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gonadotropin-Releasing Hormone (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Hormone Antagonists (pharmacology)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Insulin-Like Growth Factor II (genetics, metabolism)
• Male
• Mice
• Mice, Nude
• Neoplasms, Experimental (metabolism)
• Prostatic Neoplasms (metabolism)
• RNA, Messenger (genetics)
• Tumor Cells, Cultured