Effects of SC-560 in Combination with Cisplatin or Taxol on Angiogenesis in Human Ovarian Cancer Xenografts

This study was designed to evaluate the effect of cyclooxygenase-1 (COX-1) inhibitor, SC-560, combined with cisplatin or taxol, on angiogenesis in human ovarian cancer xenografts. Mice were treated with intraperitoneal (i.p.) injections of SC-560 6 mg/kg/day, i.p. injections of cisplatin 3 mg/kg every other day and i.p. injections of taxol 20 mg/kg once a week for 21 days. Vascular endothelial growth factor (VEGF) mRNA levels were detected by reverse transcription-polymerase chain reaction (RT-PCR); microvessel density (MVD) was determined by immunohistochemistry; and prostaglandin E(2) (PGE(2)) levels were determined using ELISA. Expression levels of VEGF mRNA and MVD in treatment groups were inhibited significantly when compared with the control group (p < 0.05 for all), and SC-560 combined with cisplatin displayed a greater reduction in the expression of VEGF and MVD than SC-560 or cisplatin alone (p < 0.05). SC-560 combined with taxol showed a greater inhibition on VEGF mRNA expression than SC-560 or taxol alone (p < 0.05). The level of PGE(2) in treatment groups was significantly reduced when compared with the control group (p < 0.01 for all). These findings may indicate that cisplatin or taxol supplemented by SC-560 in human ovarian cancer xenografts enhances the inhibition effect of cisplatin or taxol alone on angiogenesis.