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

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.

• Authors: Jörg B Engel, Andrew V Schally, Gabor Halmos, Benjamin Baker, Attila Nagy, Gunhild Keller
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 41 Issue 12 Pg. 1824-30 (Aug 2005) ISSN: 0959-8049 [Print] England
• PMID: 16051478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AN 215
• ATP Binding Cassette Transporter, Subfamily B
• Antineoplastic Agents
• RNA, Messenger
• Receptors, Bombesin
• Doxorubicin
• Bombesin

Topics

• ATP Binding Cassette Transporter, Subfamily B (metabolism)
• Animals
• Antineoplastic Agents (adverse effects, therapeutic use)
• Bombesin (adverse effects, analogs & derivatives, therapeutic use)
• Cell Line, Tumor
• Doxorubicin (adverse effects, analogs & derivatives, therapeutic use)
• Drug Resistance, Multiple
• Endometrial Neoplasms (drug therapy, metabolism)
• Female
• Humans
• Mice
• Mice, Nude
• RNA, Messenger (metabolism)
• Receptors, Bombesin (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (methods)