Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits growth of OV-1063 human epithelial ovarian cancers in nude mice.
OBJECTIVE
The aim of the study was to investigate the effects of the cytotoxic analog of luteinizing hormone-releasing hormone AN-207 on the growth of the OV-1063 human epithelial ovarian cancers, which express luteinizing hormone-releasing hormone receptor. AN-207 consists of doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) linked with the carrier [D-lysine6 ]luteinizing hormone-releasing hormone.


METHODS
Female nude mice bearing xenografts of OV-1063 ovarian cancers were treated with analog AN-207, cytotoxic radical AN-201, or agonist [D-lysine6 ]luteinizing hormone-releasing hormone. The levels and expression of messenger ribonucleic acid of receptors for luteinizing hormone-releasing hormone and epidermal growth factor were evaluated.


RESULTS
The growth of OV-1063 tumor was significantly inhibited by 3 to 5 nmol AN- 207 but not by [D-lysine6 ]luteinizing hormone-releasing hormone. Cytotoxic radical AN-201 was toxic at these doses. After treatment with AN-207 receptors for luteinizing hormone-releasing hormone were not detectable, epidermal growth factor receptor levels declined, and expressions of their respective messenger ribonucleic acids were decreased.


CONCLUSIONS
Targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207 is less toxic than equimolar doses of its radical 2-pyrrolinodoxorubicin and effectively inhibits ovarian tumor growth. Targeted chemotherapy may improve management of ovarian cancer.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011966:Receptors, LHRH / Q000235:genetics; D014407:Tumor Cells, Cultured