Experimental therapy of human endometrial cancers with a targeted cytotoxic bombesin analog AN-215: Low induction of multidrug resistance proteins

Jörg B. Engel, Andrew V. Schally, Gabor Halmos, Benjamin Baker, Attila Nagy, Gunhild Keller

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

In this study we have investigated the efficacy and toxicity of targeted cytotoxic bombesin (BN) analog AN-215 and its effects on the expression of three multidrug resistance proteins in experimental human endometrial cancers. Nude mice bearing HEC-1A, RL-95-2 and AN3CA tumours were treated with AN-215 and its cytotoxic radical (AN-201). The BN receptor expression in tumours was followed by RT-PCR analysis and radioligand binding assays. Expression of drug resistance proteins MDR-1, MRP-1 and BCRP were measured by realtime PCR. AN-215 significantly (P < 0.05) inhibited the growth of HEC-1A, RL-95-2 and AN3CA tumours while AN-201 was ineffective. The expression of BN receptors was demonstrated in all three tumour models. AN-215 caused a lower induction of MDR-1 in HEC-1A and RL-95-2 cancers than AN-201. MRP-1 and BCRP were not induced by AN-215 or AN-201. Thus, targeted chemotherapy with AN-215 powerfully inhibits the growth of human BN receptor-positive endometrial cancers.

Original languageEnglish (US)
Pages (from-to)1824-1830
Number of pages7
JournalEuropean Journal of Cancer
Volume41
Issue number12
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Keywords

  • Bombesin/GRP receptor
  • Endometrial cancer
  • Multidrug resistance
  • Targeted chemotherapy
  • Targeted cytotoxic bombesin analog AN-215

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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