[Show abstract][Hide abstract] ABSTRACT: The present study aimed to investigate the combined effects of Taxol and cyclooxygenase (COX) inhibitors on angiogenesis and cell apoptosis of SKOV-3 human ovarian carcinoma cell xenograft-bearing mice. The experiments were continued for 28 days. Animals were treated with 3 mg/kg SC-560 (a COX-1-selective inhibitor) alone, 100 mg/kg celecoxib (a COX-2-selective inhibitor) alone or SC-560/celecoxib by gavage twice a day, 20 mg/kg Taxol alone intraperitoneally once a week or in combination with SC-560 or celecoxib or SC-560/celecoxib/Taxol for three weeks. The mRNA levels of vascular endothelial growth factor (VEGF) was determined by reverse transcription-polymerase chain reaction (RT-PCR). The microvessel density (MVD) of ovarian carcinoma was determined by immunohistochemistry with anti-CD(34) as the label. The apoptotic index was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. The MVD value and apoptotic index in the SC-560/Taxol group were notably inhibited compared with the Taxol group (P<0.001). Moreover, the VEGF mRNA levels, MVD value and apoptotic index in the SC-560/Taxol group were significantly different from the celecoxib/Taxol group (P<0.05, P<0.05 and P<0.001, respectively). The present study demonstrated that SC-560 enhances the anti-angiogenic and pro-apoptotic effects of Taxol and these effects are better than with celecoxib.
[Show abstract][Hide abstract] ABSTRACT: The present study was designed to investigate whether cyclooxygenase (COX) inhibitors (coxibs) could prolong survival time by attenuating the tumor growth of ovarian cancer xenograft-bearing mice. Tumor growth and survival time were observed and compared in mice which were treated with a COX-1 inhibitor (SC-560) and a COX-2 inhibitor (celecoxib) every other day for a 21 day period from the day of tumor formation. The trial lasted a total of 121 days. The combination therapy resulted in statistically significant inhibition of tumor size compared with the control group (P<0.05). Additionally, single treatment of SC-560 or celecoxib significantly prolonged the mean survival time of mice compared with the control group (P<0.05). We suggest that COX-1 and COX-2 inhibitors may improve survival and inhibit tumor growth, and that the tumor growth inhibition by coxibs may be the contributing factor for the prolonged survival time in mouse xenograft models.
[Show abstract][Hide abstract] ABSTRACT: The present study was designed to investigate the effects of cyclooxygenase (COX) inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor) alone, 3 mg/kg SC-560 (a COX-1 selective inhibitor) alone by gavage twice a day, 20 mg/kg taxol alone by intraperitoneally (i.p.) once a week, or celecoxib/taxol, SC-560/celecoxib, SC-560/taxol or SC-560/celecoxib/taxol, for three weeks. To test the mechanism of the combination treatment, the index of cell proliferation and expression of cyclin D1 in tumor tissues were determined by immunohistochemistry. 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); downregulated cell proliferation and cyclin D1 expression were statistically significant compared with those of the control group (both p < 0.01). This study suggests that the effects of COX selective inhibitors on the growth of tumors and decreased cell proliferation in a SKOV-3 cells mouse xenograft model were similar to taxol. The three-drug combination showing a better decreasing tendency in growth-inhibitory effect during the experiment may have been caused by suppressing cyclin D1 expression.
International Journal of Molecular Sciences 12/2012; 13(8):9741-53. DOI:10.3390/ijms13089741 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to investigate the effects of a cyclooxygenase (COX)-1 inhibitor, SC-560, administered in combination with taxol, on the molecular mechanisms of antitumor efficacy in a SKOV-3 human ovarian carcinoma cell xenograft-bearing mouse model. The mice were treated with 6 mg/kg/day SC-560 by gavage twice every other day and 20 mg/kg taxol by intraperitoneal injection once a week for three weeks. 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. The index of proliferating and apoptotic cells in the tumor tissues was determined by staining for Ki-67 and using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, respectively. On day 7 after the end of administration, the tumor volume of mice in the combination group was reduced by 55.35% compared with that of the control mice, and the difference was statistically significant (P<0.05). In the combination group, the expression of VEGF, MVD and the cell proliferation index were inhibited significantly, while the apoptotic index was notably increased (all P<0.01, compared with the control group). Our results indicate that the molecular mechanisms of the antitumor efficacy of SC-560 combined with taxol therapy may act in part by inhibiting tumor angiogenesis, reducing cell proliferation and inducing cell apoptosis.