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

Masahiro Miyazaki, Andrew V. Schally, Attila Nagy, Najib Lamharzi, Gabor Halmos, Karoly Szepeshazi, Patricia Armatis

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

OBJECTIVE: 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.

Original languageEnglish (US)
Pages (from-to)1095-1103
Number of pages9
JournalAmerican journal of obstetrics and gynecology
Volume180
Issue number5
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Cytotoxic luteinizing hormone-releasing hormone analog
  • Epidermal growth factor
  • Nude mice
  • Ovarian cancer
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

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