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Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits growth of OV-1063 human epithelial ovarian cancers in nude mice.

AbstractOBJECTIVE:
The aim of the study was to investigate the effects of the cytotoxic analog of luteinizing hormone-releasing hormone AN-207 on the growth of the OV-1063 human epithelial ovarian cancers, which express luteinizing hormone-releasing hormone receptor. AN-207 consists of doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) linked with the carrier [D-lysine6 ]luteinizing hormone-releasing hormone.
STUDY DESIGN:
Female nude mice bearing xenografts of OV-1063 ovarian cancers were treated with analog AN-207, cytotoxic radical AN-201, or agonist [D-lysine6 ]luteinizing hormone-releasing hormone. The levels and expression of messenger ribonucleic acid of receptors for luteinizing hormone-releasing hormone and epidermal growth factor were evaluated.
RESULTS:
The growth of OV-1063 tumor was significantly inhibited by 3 to 5 nmol AN- 207 but not by [D-lysine6 ]luteinizing hormone-releasing hormone. Cytotoxic radical AN-201 was toxic at these doses. After treatment with AN-207 receptors for luteinizing hormone-releasing hormone were not detectable, epidermal growth factor receptor levels declined, and expressions of their respective messenger ribonucleic acids were decreased.
CONCLUSIONS:
Targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207 is less toxic than equimolar doses of its radical 2-pyrrolinodoxorubicin and effectively inhibits ovarian tumor growth. Targeted chemotherapy may improve management of ovarian cancer.
AuthorsM Miyazaki, A V Schally, A Nagy, N Lamharzi, G Halmos, K Szepeshazi, P Armatis
JournalAmerican journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 180 Issue 5 Pg. 1095-103 (May 1999) ISSN: 0002-9378 [Print] United States
PMID10329861 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Antineoplastic Agents
  • RNA, Messenger
  • Receptors, LHRH
  • AN 207
  • Gonadotropin-Releasing Hormone
  • Doxorubicin
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • ErbB Receptors
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Cell Division (drug effects)
  • Cystadenocarcinoma, Papillary (drug therapy, pathology)
  • Doxorubicin (analogs & derivatives, therapeutic use)
  • ErbB Receptors (genetics)
  • Female
  • Glyceraldehyde-3-Phosphate Dehydrogenases (genetics)
  • Gonadotropin-Releasing Hormone (analogs & derivatives, therapeutic use)
  • Humans
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Transplantation
  • Ovarian Neoplasms (drug therapy, pathology)
  • RNA, Messenger (analysis)
  • Receptors, LHRH (genetics)
  • Tumor Cells, Cultured

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