mobic and Peritoneal-Neoplasms

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.. 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).. 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.. These results indicate that both meloxicam and ciglitazone produce antitumor effects against ovarian cancer in conjunction with reduced angiogenesis and induction of apoptosis.

Topics: Animals; Apoptosis; Ascites; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Female; Humans; Immunohistochemistry; Intramolecular Oxidoreductases; Meloxicam; Mice; Mice, Inbred BALB C; Mice, Nude; Ovarian Neoplasms; Peritoneal Neoplasms; PPAR gamma; Prostaglandin-E Synthases; Survival Analysis; Thiazines; Thiazoles; Thiazolidinediones; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

Many reports have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) suppress malignant transformation and tumor growth, and some NSAIDs are expected to be new anti-cancer agents. In this study, we examined the anti-tumor effects of the non-specific cyclooxygenase (COX) inhibitors aspirin and piroxicam, and the selective COX-2 inhibitor meloxicam on xenotransplanted ovarian cancer. Tumor growth and survival were compared in female nu/nu mice, xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors and treated with aspirin (200 ppm in diet, everyday), piroxicam (150 ppm in diet, everyday) or meloxicam (162 ppm in diet, everyday). Al, of the agents tested significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously as compared to the control. There was a significant difference in inhibition of OVCAR-3 tumor growth between meloxicam and aspirin treatment. Meloxicam and piroxicam treatment significantly prolonged survival of mice with malignant ascites derived from DISS cells as compared to control and aspirin treatment. Mice treated with meloxicam survived significantly longer than those treated with piroxicam. There was no significant difference in survival between control and aspirin treatment. Necropsy revealed that one of the 6 cancer-bearing mice treated with piroxicam suffered from stomach perforation. These results indicate that a selective COX-2 inhibitor produces greater anti-tumor effect against ovarian cancer than a nonselective COX inhibitor and that meloxicam may have a potential of leading to a novel therapeutic strategy against ovarian cancer.

Topics: Animals; Aspirin; Carcinoma; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Female; Humans; Meloxicam; Mice; Mice, Inbred BALB C; Ovarian Neoplasms; Peritoneal Neoplasms; Piroxicam; Thiazines; Thiazoles; Xenograft Model Antitumor Assays