Luteinizing hormone-releasing hormone antagonist cetrorelix (SB-75) and bombesin antagonist RC-3940-11 inhibit the growth of androgen-independent PC- 3 prostate cancer in nude mice

Andreas Jungwirth, Georg Galvan, Jacek Pinski, Gabor Halmos, Karoly Szepeshazi, Renzhi Cai, Kate Groot, Andrew V. Schally

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

BACKGROUND. Hormones like bombesin (BN)/gastrin-releasing peptide (GRP) and luteinizing hormone-releasing hormone (LH-RH) and growth factors such as epidermal growth factor (EGF) might be involved in the relapse of prostate cancer under androgen ablation therapy. Interference with receptors for BN/GRP, LH-RH, or EGF might provide a therapeutic approach to inhibit tumor growth of androgen-independent prostate cancer. METHODS. LH-RH antagonist Cetrorelix (SB-75) and the BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the androgen-independent PC-3 human prostate cancer cell line xenografted into nude mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP and EGF were measured. RESULTS. When the treatment was started, tumor volume in all groups was 70-80 mm3. After 4 weeks, tumor volume in the control animals injected with saline was 871 ± 233 mm3 and that of animals treated with Cetrorelix only 197 ± 61 mm3. The BN/GRP antagonist RC-3940-II also significantly reduced PC-3 tumor volume in nude mice to 122 ± 20 mm3. The combination of Cetrorelix and RC-3940-II produced no additional inhibition. High-affinity receptors for EGF were detected in the tumor membranes and their number was significantly decreased after administration of Cetrorelix or RC-3940-II. CONCLUSIONS. These findings demonstrate that LH-RH antagonists and BN/GRP antagonists inhibit the growth of the androgen-independent prostate cancer cell line PC-3 in vivo. Both analogs may exert a direct inhibitory effect on tumor growth through a down- regulation of EGF receptors.

Original languageEnglish (US)
Pages (from-to)164-172
Number of pages9
JournalProstate
Volume32
Issue number3
DOIs
StatePublished - Aug 1 1997
Externally publishedYes

Keywords

  • Bombesin antagonist
  • Cetrorelix
  • LH-RH antagonist
  • Nude mouse
  • PC-3 tumor
  • Peptide antagonists
  • Prostatic cancer
  • Xenografts

ASJC Scopus subject areas

  • Urology

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