Effective treatment of experimental androgen sensitive and androgen independent intraosseous prostate cancer with targeted cytotoxic somatostatin analogue AN-238

Markus Letsch, Andrew V. Schally, Karoly Szepeshazi, Gabor Halmos, Attila Nagy

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Purpose: The targeted cytotoxic somatostatin analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to carrier octapeptide RC-121, is scheduled for clinical trials. To extend previous findings we tested AN-238 on human androgen sensitive MDA-PCa-2b prostate cancers grown subcutaneously and androgen independent LNCaP derived C4-2 prostate cancers xenografted into the tibiae of nude mice. Materials and Methods: Changes in serum prostate specific antigen (PSA) levels were monitored by radioimmunoassay. Somatostatin receptors in tumor samples were characterized. Results: Three intravenous injections of AN-238 at 150 nmol/kg doses inhibited the growth of subcutaneous MDA-PCa-2b tumors by 62% vs controls (p < 0.05) and were more effective than equimolar doses of the radical AN-201 (p < 0.05). AN-238 also decreased serum PSA levels by 62% vs controls (p < 0.01). In nude mice bearing intra-osseous implanted C4-2 prostate cancers AN-238 decreased serum PSA levels by 65% compared with controls after 5 weeks of therapy (p < 0.05), while AN-201 was ineffective. All AN-238 treated mice were alive at the termination of the experiment, while only 50% of controls and 60% of animals treated with AN-201 survived (p < 0.01). Histological evaluation of intraosseous C4-2 tumors showed that AN-238 induced a significant increase in apoptosis (p < 0.05). MDA-PCa-2b and C4-2 tumors showed high affinity binding for somatostatin and the expression of mRNA for somatostatin receptor subtypes 1, 2A and 5. Conclusions: The current study demonstrates the efficacy of the somatostatin analogue AN-238 for subcutaneous MDA-PCa-2b as well as for intraosseous C4-2 prostate cancers xenografted into nude mice. This targeted cytotoxic analogue could represent a new therapy for patients with advanced metastatic prostate carcinoma.

Original languageEnglish (US)
Pages (from-to)911-915
Number of pages5
JournalJournal of Urology
Volume171
Issue number2 I
DOIs
StatePublished - Feb 2004

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Keywords

  • Bone metastases
  • Prostate
  • Prostatic neoplasms
  • Somatostatin
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Urology

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