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. Design: 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. Setting: Experimental laboratory research. Animal(s): Female athymic nude mice (Ncr, nu/nu). Intervention(s): 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. Main Outcome Measure(s): Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count. and LHRH receptor expression. Result(s): 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. Conclusion(s): 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.