Complete regression of MX-1 human breast carcinoma xenografts after targeted chemotherapy with a cytotoxic analog of luteinizing hormone- releasing hormone, AN-207

Zsuzsanna Kahán, Attila Nagy, Andrew V. Schally, Gábor Halmos, José M. Arencibia, Kate Groot

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in about 50% of human breast carcinomas. A highly potent cytotoxic agent, 2-pyrrolinodoxorubicin (AN-201), was linked to the agonist [D- Lys6]LH-RH to form a cytotoxic LH-RH analog, AN-207, that can be targeted to LH-RH receptors on breast carcinomas. METHODS. Nude mice bearing MX-1 hormone-independent, doxorubicin-resistant human breast carcinomas were injected intravenously with vehicle (control), 250 nmol/kg doses of AN-201, AN-207, or an unconjugated mixture of AN-201 and [D-Lys6]LH-RH. Tumor growth and changes in hematologic parameters were evaluated. Receptors for LH-RH were investigated by radioreceptor assays, and the expression of their mRNA was determined by reverse transcriptase-polymerase chain reaction. RESULTS. AN-207 caused complete regression of MX-1 tumors in all 10 animals, and they were still tumor free 60 days after treatment. In contrast, after therapy with AN-201 or the mixture of AN-201 and [D-Lys6]LH-RH, the regression of most MX-1 tumors was only transitory. AN-201 caused the death of 1 of the 10 animals and significantly greater leukopenia than AN-207, which produced no toxic deaths. Radioreceptor assays revealed high affinity binding sites for LH-RH on tumor cell membranes. The expression of mRNA for LH-RH receptors also was found in tumors. CONCLUSIONS. The results of this study indicate thai powerful, targeted cytotoxic LH-RH analogs such as AN-207 could be considered for the treatment of human breast carcinomas that possesses receptors for LH-RH.

Original languageEnglish (US)
Pages (from-to)2608-2615
Number of pages8
JournalCancer
Volume85
Issue number12
DOIs
StatePublished - Jun 15 1999
Externally publishedYes

Keywords

  • Breast carcinoma
  • Cytotoxic LH-RH analog
  • MX-1 human breast carcinoma xenograft
  • Receptor targeted chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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