Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207.
OBJECTIVE
To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207.


METHODS
Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expression of LHRH receptors in HEC-1A and RL-95-2 cancers was determined by reverse transcription-polymerase chain reaction, Western blot analysis, and radioligand binding assays.


METHODS
Experimental laboratory research.


METHODS
Female athymic nude mice (Ncr, nu/nu).


METHODS
Animals were treated with IV injections of the cytotoxic LHRH analogues AN-152 and AN-207 and their respective cytotoxic radicals doxorubicin (DOX) and AN-201 (2-pyrrolinodoxorubicin) on a control vehicle solution.


METHODS
Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count, and LHRH receptor expression.


RESULTS
AN-152 significantly inhibited the growth of HEC-1A tumors. AN-207 also significantly suppressed the proliferation in vivo of HEC-1A and RL-95-2 cancers. The cytotoxic radicals DOX and AN-201 had no effect. Furthermore, mRNA for LHRH receptors, LHRH receptor protein, and high-affinity binding sites for LHRH were demonstrated on tumors.


CONCLUSIONS
Targeted chemotherapy with AN-152 and AN-207 strongly inhibits the growth of human endometrial cancers, which express LHRH receptors, and could provide a new treatment modality for women with advanced endometrial carcinoma.
Engel
Jörg B
JB
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70112-1262, USA.
Keller
Gunhild
G
Schally
Andrew V
AV
Nagy
Attila
A
Chism
David D
DD
Halmos
Gabor
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D011966:Receptors, LHRH; C104648:AN 207; C080883:LHRH, lysine(6)-doxorubicin; D007987:Gonadotropin-Releasing Hormone; D004317:Doxorubicin