title: Minocycline inhibits malignant ascites of ovarian cancer through targeting multiple signaling pathways.
abstract: OBJECTIVE
  To evaluate the effect of minocycline on the expression of cytokines and growth factors responsible for malignant ascite formation.
  
  
  METHODS
  In vitro, cells obtained from malignant ascites were pre-treated with minocycline (0-100 μmol/L) and exposed briefly to hypoxia. In vivo, female nude mice bearing OVCAR-3 tumors were treated orally in drinking water with minocycline for 4 weeks. Plasma, ascites, and tumors were analyzed.
  
  
  RESULTS
  Minocycline blocked hypoxia-induced surge in interleukin-6 (IL-6), its soluble receptor (sIL-6R) and vascular endothelial growth factor (VEGF) levels in concentration-dependent manner. In mice, orally administered minocycline led to dramatic reduction in tumor weight and malignant ascite volume. IL-6, sIL6R and in particular VEGF levels were highly suppressed in plasma, ascite fluid and tumor tissue by minocycline. In addition, tumors from minocycline treated mice expressed profoundly lower levels of phosphorylated extracellular regulated kinases (p-Erk1/2) and p-Akt. Minocycline was also effective at suppressing transforming growth factor beta (TGF-β1) and increasing vascular endothelial cadherin (VE-cadherin) expression thereby providing molecular confirmation for its effects on malignant ascite formation.
  
  
  CONCLUSIONS
  Orally administered minocycline is highly effective in suppressing ovarian cancer-induced malignant ascites by targeting cytokines and growth factors essential for tumor growth and malignant ascite formation.
authors.affiliation: Cancer Research Laboratories, Department of Surgery, St George Hospital, University of New South Wales, Sydney, Australia. mh.pourgholami@unsw.edu.au
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Pourgholami
authors.forename: Parvin
authors.initials: P
authors.lastname: Ataie-Kachoie
authors.forename: Samina
authors.initials: S
authors.lastname: Badar
authors.forename: David Lawson
authors.initials: DL
authors.lastname: Morris
mesh_terms: D000818:Animals; D001201:Ascites / Q000188:drug therapy* / Q000209:etiology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000097:blood; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D015850:Interleukin-6; D008911:Minocycline; D051057:Proto-Oncogene Proteins c-akt; D019947:Receptors, Interleukin-6; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000093242:Interleukin-6 Inhibitors