title: The antitumor efficacy of cisplatin in combination with triptorelin and exemestane therapy for an ovarian cancer ascites model in Wistar rats.
abstract: OBJECTIVE
  To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant transplantable ascites ovarian tumor (OT); to assess tumor response to treatment and VEGF expression in tumor cells under different combinations of cytostatic and hormonal drugs.
  
  
  METHODS
  36 female Wistar rats, which underwent intraperitoneal transplantation of ascites OT (5×10(6) cells per animal), have been involved in the study. Rats were distributed into 4 groups (9 rats in each group): group 1 - animals, which received combination of cisplatin and triptorelin; group 2 - rats treated with combination of cisplatin and exemestane; group 3 - animals, which were administered with combination of cisplatin, triptorelin and exemestane; group 4 - rats, which received combination of triptorelin and exemestane. Histological study with assessment of treatment pathomorphosis in OT and immunohistochemical study have been carried out to analyze VEGF expression in OT cells. Survival of animals has been evaluated.
  
  
  RESULTS
  Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly higher rates of treatment pathomorphosis (10.1 ± 0.1% and 16.2 ± 0.3%, respectively) and antiangiogenic activity in OT (21.4 ± 1.4% and 15.0 ± 1.3%, respectively), as well as the highest survival of animals (100.0 and 85.7%, respectively) as compared with the same in rats treated in regimen of monotherapy with cisplatin, triptorelin, exemestane or by combination of hormonal drugs. Among animals treated by combination of cytostatic drug with triptorelin, two were cured (22.2%), and among rats, which received cisplatin and exemestane, one animal (11.1%) was cured.
  
  
  CONCLUSIONS
  Triptorelin and exemestane increase antitumor activity of cisplatin in respect to the transplantable malignant ascites OT and significantly increase survival of animals, especially when triptorelin and cisplatin are used in combination.
authors: National Cancer Institute, Kyiv, 03022, Ukraine.
authors: I G
authors: IG
authors: Tkalia
authors: National Cancer Institute, Kyiv, 03022, Ukraine.
authors: L I
authors: LI
authors: Vorobyova
authors: National Cancer Institute, Kyiv, 03022, Ukraine.
authors: A N
authors: AN
authors: Grabovoy
authors: National Cancer Institute, Kyiv, 03022, Ukraine.
authors: V S
authors: VS
authors: Svintsitsky
authors: National Cancer Institute, Kyiv, 03022, Ukraine.
authors: T O
authors: TO
authors: Tarasova
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001201:Ascites / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D017329:Triptorelin Pamoate; C056516:exemestane; D002945:Cisplatin