Inhibition of growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog

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

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objectives: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. Methods: Nude mice with xenografts of Pane-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. Results: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. Conclusions: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalPancreas
Volume31
Issue number3
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

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Keywords

  • Bombesin/gastrin-releasing peptide receptor
  • Cytotoxic bombesin analog
  • Pancreatic carcinoma
  • Targeted cancer therapy

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

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