Background Chemotherapy in combination with taxol is the standard first-line therapy for patients with advanced ovarian cancer. It is often assumed that the antitumor effects of nonsteroidal anti-inflammatory drugs are due to inhibition of cyclooxgenase (COX) activity.
Aim To investigate the effects of taxol in combination with cyclooxygenase inhibitors on the expression of cyclin D1 and angiogenesis in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice.
Methods The animals were treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor) alone or in combination with 3 mg/kg SC-560 (a COX-1 selective inhibitor) by gavage twice a day, 20mg/kg taxol alone by intraperitoneal (i.p.) once a week or in combination with celecoxib, or SC-560/celecoxib/taxol for three weeks. To test the mechanism of the combination treatment, expression of cyclin D1 in tumor tissues were determined by immunohistochemistry. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) mRNA levels of ovarian cancer were detected in the tumor tissues using immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) respectively.
Results The mean tumor volume in the treated groups was significantly lower than control (p < 0.05), and in the three-drug combination group, tumor volume was reduced by 58.27% (p < 0.01); cyclin D1 expression were statistically significant compared with those of the control group (both p < 0.01). In the combination group, the expression of VEGF and MVD were inhibited significantly (all p < 0.01, compared with control).
Conclusions This study suggests that COX selective inhibitors in combination with taxol may be superior than taxol alone as drug therapy against ovarian cancer xenografts. It may in part be mediated through suppression of cyclin D1, which may contribute to its ability to arrest the cell cycle, and that antiangiogenic therapy can be used to inhibit ovarian cancer growth.