In vivo studies of the new gonadotropin-releasing hormone antagonist--copolymer conjugates having antitumor activity.

The aim of the study was to test in vivo the gonadotropin-releasing hormone (GnRH) antagonists and their conjugates showing antitumor activities in vitro. The in vivo experiments with the human GnRH antagonist MI-1544 (Ac-D-Trp1,3,D-Cpa2,D-Lys6,D-Ala10)-GnRH, the chicken GnRH antagonist MI-1892 (Ac-D-Trp1,3,D-Cpa2,Lys5,/beta-Asp(DEA)/6,Gln8,D-Al a10)-GnRH, and their copolymer conjugates were carried out on MCF-7 and MDA-MB-231 human breast tumors xenografted in immunosuppressed CBA/Ca HRIJ-T6 female mice and on MXT mouse mammary tumors in BDF1 mice. The P-X-1544 and P-X-1892 conjugates were prepared by coupling the GnRH antagonists to macromolecule copolymer through biodegradable spacers. MI-1544 and its conjugate had strong, whereas MI-1892 and its conjugate had slight, castration effect in rats. All of them showed selective antitumor activity. The conjugates, given daily, inhibited both types of xenografts by 42 to 49%. Their activity was stronger in MXT mammary tumor (72 to 61%). The in vivo effect of GnRH antagonists was largely increased by coupling them to nonbiodegradable macromolecule carriers of polyanionic character. P-X-1544 and P-X-1892 GnRH antagonist-macromolecule conjugates might become important therapeutic agents for the treatment of breast cancer.
AuthorsB Vincze, I Pályi, D Gaál, J Pató, M Móra, I Mezõ, I Teplán, J Seprõdi
JournalCancer detection and prevention (Cancer Detect Prev) Vol. 20 Issue 2 Pg. 153-9 ( 1996) ISSN: 0361-090X [Print] UNITED STATES
PMID8706041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Hormonal
  • Drug Carriers
  • Hormone Antagonists
  • MI 1892
  • P-X 1544
  • P-X 1892
  • Gonadotropin-Releasing Hormone
  • MI 1544
  • Animals
  • Antineoplastic Agents, Hormonal (therapeutic use)
  • Breast Neoplasms (drug therapy)
  • Disease Progression
  • Drug Carriers
  • Female
  • Gonadotropin-Releasing Hormone (analogs & derivatives, antagonists & inhibitors, pharmacology, therapeutic use)
  • Hormone Antagonists (therapeutic use)
  • Humans
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Inbred CBA
  • Neoplasm Transplantation
  • Thymectomy
  • Transplantation, Heterologous

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