Therapy of experimental hepatic cancers with cytotoxic peptide analogs targeted to receptors for luteinizing hormone-releasing hormone, somatostatin or bombesin

Karoly Szepeshaz, Andrew V. Schally, Andrea Treszl, Stephan Seitz, Gabor Halmos

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

As there is no effective systemic therapy for advanced hepatocellular carcinoma (HCC), we investigated the presence of receptors for somatostatin, bombesin and luteinizing hormone-releasing hormone (LHRH) in SK-Hep1 human hepatic carcinoma and the effects of cytotoxic analogs of somatostatin (AN-238), bombesin (AN-215) and LHRH (AN-207) on the growth of this tumor. Nude mice bearing SK-Hep-1 HCCs were treated with AN-238, AN-215, AN-207 and their combination, or cytotoxic radical 2-pyrrolinodoxorubicin (AN-201). Tumor growth reduction was determined and cell proliferation characteristics and apoptosis were studied by histologic analysis. The expression of receptors for somatostatin, bombesin and LHRH was investigated by radioreceptor assays and immunohistochemistry. High-affinity binding sites for somatostatin, bombesin and LHRH were detected in SK-Hep-1 cancers. All three cytotoxic peptide analogs inhibited growth of SK-Hep-1 tumors and decreased the cell proliferation rate. Combination therapy with two or three cytotoxic analogs resulted in the strongest tumor inhibition. Receptors for somatostatin, bombesin and LHRH are expressed in SK-Hep-1 human HCC. Cytotoxic peptide analogs targeted to these receptors inhibit growth of this tumor. Targeting to multiple receptors enhances the efficacy of therapy. The results of our study encourage additional experimental investigations to permit the introduction of these cytotoxic analogs into clinical trials.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalAnti-Cancer Drugs
Volume19
Issue number4
DOIs
StatePublished - Apr 1 2008

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Keywords

  • Cytotoxic bombesin
  • Cytotoxic luteinizing hormone-releasing hormone
  • Cytotoxic somatostatin
  • SK-Hep-1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research
  • Oncology

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