title: Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage: an experimental study with nu/nu athymic mice.
abstract: OBJECTIVE
  Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage.
  
  
  METHODS
  nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH).
  
  
  RESULTS
  Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05).
  
  
  CONCLUSIONS
  Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
authors.forename: Qiong-yan
authors.initials: QY
authors.lastname: Lin
authors.forename: Yi-feng
authors.initials: YF
authors.lastname: Wang
authors.forename: Hui-nan
authors.initials: HN
authors.lastname: Weng
authors.forename: Xiu-jie
authors.initials: XJ
authors.lastname: Sheng
authors.forename: Qing-ping
authors.initials: QP
authors.lastname: Jiang
authors.forename: Zhi-ying
authors.initials: ZY
authors.lastname: Yang
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004347:Drug Interactions; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects*; D011897:Random Allocation; D017329:Triptorelin Pamoate / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D016328:NF-kappa B; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D054304:Anti-Mullerian Hormone; D053148:Caspase 3; D002945:Cisplatin