title: Antitumor effects of cecropin B-LHRH' on drug-resistant ovarian and endometrial cancer cells.
abstract: BACKGROUND
  Luteinizing hormone-releasing hormone receptor (LHRHr) represents a promising therapeutic target for treating sex hormone-dependent tumors. We coupled cecropin B, an antimicrobial peptide, to LHRH', a form of LHRH modified at carboxyl-terminal residues 4-10, which binds to LHRHr without interfering with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. This study aimed to assess the antitumor effects of cecropin B-LHRH' (CB-LHRH') in drug-resistant ovarian and endometrial cancers.
  
  
  METHODS
  To evaluate the antitumor effects of CB-LHRH', three drug resistant ovarian cancer cell lines (SKOV-3, ES-2, NIH:OVCAR-3) and an endometrial cancer cell line (HEC-1A) were treated with CB-LHRH'. Cell morphology changes were assessed using inverted and electron microscopes. In addition, cell growth and cell cytotoxicity were measured by MTT assay and LDH release, respectively. In addition, hemolysis was measured. Furthermore, radioligand receptor binding, hypersensitization and minimal inhibitory concentrations (against Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were determined. Finally, the impact on tumor growth in BALB/c-nu mice was assessed in an ES-2 xenograft model.
  
  
  RESULTS
  CB-LHRH' bound LHRHr with high-affinity (dissociation constant, Kd = 0.252 ± 0.061 nM). Interestingly, CB-LHRH' significantly inhibited the cell viability of SKOV-3, ES-2, NIH:OVCAR-3 and HEC-1A, but not that of normal eukaryotic cells. CB-LHRH' was active against bacteria at micromolar concentrations, and caused no hypersensitivity in guinea pigs. Furthermore, CB-LHRH' inhibited tumor growth with a 23.8 and 20.4 % reduction in tumor weight at 50 and 25 mg/kg.d, respectively.
  
  
  CONCLUSIONS
  CB-LHRH' is a candidate for targeted chemotherapy against ovarian and endometrial cancers.
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.affiliation: Central Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Women Health Care, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Pharmacy Division, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Pharmacy Division, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. xinmeizhangsci@126.com.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D054807:Cecropins / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D054807:Cecropins; D007987:Gonadotropin-Releasing Hormone; D004317:Doxorubicin
keywords: Cecropin B peptide; Endometrial cancer; Luteinizing hormone releasing-hormone receptor; Ovarian cancer