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. Study Design: 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. (Am J Obstet Gynecol 1999;180:1095-103.)