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

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 transferase-mediated 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.

Epithelial ovarian cancer; SC-560; Cisplatin; Taxol; Cyclin D1; Apoptosis; Vascular endothelial growth factor.

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