Inhibition of in vivo proliferation of MDA-PCa-2b human prostate cancer by a targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207

Artur Plonowski, Andrew V. Schally, Attila Nagy, Kate Groot, Magdalena Krupa, Nora M. Navone, Christopher Logothetis

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The efficacy of therapy with targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analog AN-207 consisting of superactive doxorubicin derivative AN-201 linked to carrier [d-Lys6]LH-RH was evaluated in vivo in nude mice bearing xenografts of MDA-PCa-2b prostate cancer line. AN-207 was administered intravenously (i.v.) at 200 nmol/kg on day 1 and at 150 nmol/kg on day 14. After 4 weeks of treatment with AN-207, tumor growth was inhibited as shown by a 63% (P < 0.01) decrease in tumor volume and a 55% (P < 0.05) reduction in tumor weight, compared with controls. None of the animals died after administration of AN-207 at the total dose of 350 nmol/kg, and at the end of the experiment the body weights of mice given AN-207 did not differ significantly from controls. A single injection of cytotoxic radical AN-201 at 200 nmol/kg resulted in 43% mortality. In the surviving mice, AN-201 caused a 50% inhibition in tumor volume and a 27% reduction in tumor weight, which were non-significant, as compared to the controls. After 4 weeks, serum prostate-specific antigen concentrations in mice treated with AN-207 were 65% lower than those in controls (P < 0.05), while in animals given AN-201 the reduction in serum prostate-specific antigen was only 40% (NS). The expression of mRNA for LHRH receptors was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in MDA-PCa-2b tumors. The present study indicates that chemotherapy targeted to LHRH receptors on tumors inhibits growth of MDA-PCa-2B prostate cancers representative of human carcinoma disseminated to the bone and progressing despite androgen withdrawal.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalCancer letters
Volume176
Issue number1
DOIs
StatePublished - Feb 8 2002
Externally publishedYes

Keywords

  • Luteinizing hormone-releasing hormone
  • Luteinizing hormone-releasing hormone receptors
  • Prostate cancer
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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