title: Inhibitory effect of meloxicam, a selective cyclooxygenase-2 inhibitor, and ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, on the growth of human ovarian cancers.
abstract: BACKGROUND
  It was recently reported that high expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and low expression of cyclooxygenase-2 (COX-2) might be involved in the inhibition of ovarian tumor progression and confirmed that PPARgamma activation could suppress COX-2 expression via the nuclear factor-kappaB pathway in ovarian cancer cells.
  
  
  METHODS
  The current study investigated whether meloxicam, a selective COX-2 inhibitor, and ciglitazone, a ligand for PPARgamma, inhibit the growth of human ovarian cancer cell lines and aimed to elucidate the molecular mechanism of their antitumor effect. Tumor growth and survival were examined in female nu/nu mice xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors and treated with meloxicam (162 ppm in diet, every day) or ciglitazone (15 mg/kg intraperitoneally once a week).
  
  
  RESULTS
  Both meloxicam and ciglitazone treatments significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with controls. Meloxicam treatment decreased COX-2 expression in tumors by 2.5-fold compared with that observed in untreated tumors. Although ciglitazone treatment did not alter COX-2 expression in tumors, it reduced the expression of microsomal prostaglandin (PG) E synthase, which converts COX-derived PGH(2) to PGE(2). Both meloxicam and ciglitazone decreased PGE(2) levels in serum as well as in ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated with either meloxicam or ciglitazone.
  
  
  CONCLUSIONS
  These results indicate that both meloxicam and ciglitazone produce antitumor effects against ovarian cancer in conjunction with reduced angiogenesis and induction of apoptosis.
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: Bing
authors.initials: B
authors.lastname: Xin
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Shigeto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Futagami
authors.forename: Hideki
authors.initials: H
authors.lastname: Mizunuma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001201:Ascites / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D000077239:Meloxicam; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000071876:Prostaglandin-E Synthases; D016019:Survival Analysis; D013843:Thiazines / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D047495:PPAR gamma; D013843:Thiazines; D013844:Thiazoles; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; C039671:ciglitazone; D000077239:Meloxicam