Experimental therapy of human endometrial cancers with a targeted cytotoxic bombesin analog AN-215: low induction of multidrug resistance proteins.
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.
Engel
Jörg B
JB
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70112-1262, USA.
Schally
Andrew V
AV
Halmos
Gabor
G
Baker
Benjamin
B
Nagy
Attila
A
Keller
Gunhild
G
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001839:Bombesin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D018004:Receptors, Bombesin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C416531:AN 215; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D004317:Doxorubicin; D001839:Bombesin