Anti-tumor effect of non-steroidal anti-inflammatory drugs on human ovarian cancers

摘要

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 nuu 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.