Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207

Jörg B. Engel, Gunhild Keller, Andrew V. Schally, Attila Nagy, David D. Chism, Gabor Halmos

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Objective: To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207. Design: Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expression of LHRH receptors in HEC-1A and RL-95-2 cancers was determined by reverse transcription-polymerase chain reaction, Western blot analysis, and radioligand binding assays. Setting: Experimental laboratory research. Animal(s): Female athymic nude mice (Ncr, nu/nu). Intervention(s): Animals were treated with IV injections of the cytotoxic LHRH analogues AN-152 and AN-207 and their respective cytotoxic radicals doxorubicin (DOX) and AN-201 (2- pyrrolinodoxorubicin) on a control vehicle solution. Main Outcome Measure(s): Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count, and LHRH receptor expression. Result(s): AN-152 significantly inhibited the growth of HEC-1A tumors. AN-207 also significantly suppressed the proliferation in vivo of HEC-1A and RL-95-2 cancers. The cytotoxic radicals DOX and AN-201 had no effect. Furthermore, mRNA for LHRH receptors, LHRH receptor protein, and high-affinity binding sites for LHRH were demonstrated on tumors. Conclusion(s): Targeted chemotherapy with AN-152 and AN-207 strongly inhibits the growth of human endometrial cancers, which express LHRH receptors, and could provide a new treatment modality for women with advanced endometrial carcinoma.

Original languageEnglish (US)
Pages (from-to)1125-1133
Number of pages9
JournalFertility and sterility
Volume83
Issue number4 SUPPL.
DOIs
StatePublished - Apr 2005
Externally publishedYes

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Keywords

  • Cytotoxic conjugates AN-152 and AN-207
  • Endometrial cancer
  • LHRH receptor
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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