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

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• 作者：Qiong-yan Lin (1)
  Yi-feng Wang (2)
  Hui-nan Weng (1)
  Xiu-jie Sheng (1)
  Qing-ping Jiang (1)
  Zhi-ying Yang (1)
  
• 关键词：Gonadotrophin ; releasing hormone ; Cisplatin ; Ovarian cancer ; Animal experiment ; R711.75
• 刊名：Journal of Zhejiang University SCIENCE B
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：13
• 期：11
• 页码：894-903
• 全文大小：764KB
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• 作者单位：Qiong-yan Lin (1)
  Yi-feng Wang (2)
  Hui-nan Weng (1)
  Xiu-jie Sheng (1)
  Qing-ping Jiang (1)
  Zhi-ying Yang (1)
  
  1. 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
  2. Department of Obstetrics and Gynecology, Zhujiang Hospital, Nanfang Medical University, Guangzhou, 510282, China
  
• ISSN：1862-1783

文摘

Background and 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.