Effects of a cyclooxygenase-1-selective inhibitor in combination with taxol or cisplatin on cyclin D1, apoptosis, and vascular endothelial growth factor in a xenograft model of ovarian cancer

Abstract

This study evaluated the effectiveness of SC-560 (a cyclooxygenase-1-selective inhibitor) in combination with taxol or cisplatin (DDP) in mice bearing SKOV-3 human ovarian carcinoma xenograft. Cyclin D1 expression, apoptotic index, and vascular endothelial growth factor (VEGF) mRNA level in tumor tissues were determined by immunohistochemistry, terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick end labeling assay, and reverse transcription-polymerase chain reaction, respectively. Cyclin D1 and VEGF mRNA expression were inhibited, whereas the apoptotic index was markedly increased in the therapeutic group (all p < 0.05 in comparison with the control). The group of SC-560 + taxol had synergistic effects on suppressing cyclin D1 and VEGF expression and promoting apoptosis in comparison to SC-560 or taxol alone (p < 0.05). Compared with SC-560 or DDP group, SC-560 + DDP treatment made a greater reduction on level of VEGF mRNA (p < 0.05). The results of this study revealed that the combined therapy of SC-560 and taxol had synergistic effects on suppression of cyclin D1 and VEGF expression, and apoptosis-promoting in mice bearing SKOV-3 human ovarian carcinoma xenografts.