Powerful inhibition of in-vivo growth of experimental hepatic cancers by bombesin/gastrin-releasing peptide antagonist RC-3940-II

Karoly Szepeshazi, Andrew V. Schally, Ferenc G. Rick, Norman L. Block, Irving Vidaurre, Gabor Halmos, Luca Szalontay

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Hepatic carcinoma is a major health problem worldwide. Its incidence is increasing in Western countries and there is currently no effective systemic therapy against it. Targeted treatment modalities developed in the past few years have provided very limited success. Development of new treatment strategies is therefore essential. We investigated the effects of bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC-3940-II on experimental human liver cancers in nude mice. SK-Hep-1 and Hep-G2 cancers transplanted subcutaneously into nude mice were treated daily with 10 or 20 μg of RC-3940-II. Tumor growth was monitored for 50-184 days in five experiments. Tumor gene expression was analyzed with PCR array and protein expression by immunoblotting. Characteristics of BN/GRP receptors in the tumors were analyzed by binding assays. Effects of RC-3940-II on cell proliferation were investigated in vitro. RC-3940-II inhibited the growth of SK-Hep-1 cancers in nude mice by 65-98%, with total regression in 9 of 36 tumors in three experiments. The BN/GRP antagonist inhibited the growth of Hep-G2 cancers as well by 73-82% in two experiments, being effective even on originally large tumors. Gene expression analysis showed an increase in several angiogenesis inhibitors and decrease in proangiogenic genes after RC-3940-II treatment. Receptor assays demonstrated high-affinity binding sites for BN/GRP in both tumor lines. BN/GRP antagonist RC-3940-II powerfully inhibits growth of SK-Hep-1 and Hep-G2 cancers in nude mice. Its effect may be linked to changes in expression of those cancer genes important in angiogenesis, invasion, and metastasis. RC-3940-II may be considered for further investigations in treatment of liver cancers.

Original languageEnglish (US)
Pages (from-to)906-913
Number of pages8
JournalAnti-Cancer Drugs
Volume23
Issue number9
DOIs
StatePublished - Oct 1 2012

Keywords

  • angiogenesis
  • antineoplastic agents
  • bombesin analog
  • gastrin-releasing peptide receptors
  • hepatic cancer
  • nude mice

ASJC Scopus subject areas

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

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