Effects Of SC-560 In Combination With Taxol Or Cisplatin On Expression Of Cyclin D1,apoptosis And Ki-67 Of Ovarian Cancer In Vivo

Objective:This study was designed to evaluate the effects of SC-560(a COX-1 selective inhibitor)combined with taxol or cisplatin on the expression of cyclin D1,apoptosis and cell proliferation in human ovarian SKOV-3 tumor cells xenograft-bearing mice.Methods:During 21 days,taxol and cisplatin were used to the disposed groups of mice by intra-peritoneal(i.p.)injections,SC-560 were used to the disposed groups of mice by oral gavage.The dose of cisplatin is 3 mg/kg every other day,the dose of taxol is 20 mg/kg once a week,the dose of SC-560 is 6 mg/kg/day.Expression of cyclin D1 and the indexof Ki-67 in tumor tissues were determined by immunohistochemistry.The apoptotic index was detected by TUNEL method.Result:We observed that the average size of samples in all the drug-treated mice were signif-icantly suppressed,however,the size of samples in the control group is actually in-creased throughout the period examined(p<0.05 for all).Apoptosis rate was 56.00±5.23%,53.00±3.88%,52.00±2.14%,74.00±3.44%,54.00±2.32%in SC-560,taxol,DDP,SC-560/taxol and SC-560/DDP,respectively,which was significantly improved compared with the control group(33.00 ± 8.36%,p<0.05 for all).And the combination group of SC-560 and taxol showed a synergistic influence on cell apoptosis com-pared with the single medication group of taxol(p<0.05).However,cell apoptosis in the single medication group of SC-560 or the combining group of SC-560 and DDP demonstrated no significant difference Quantification of cyclin D1-postive cells showed in control,SC-560,taxol,DDP,SC-560/taxol and SC-560/DDP was 43.00 ±6.12%,17.00± 4.23%,22.00 ± 1.94%,25.00 ± 2.13%,9.00 ± 1.44%,23.00 ± 1.87%,respectively.There was a significant inhibitory effect on groups with chemotherapeutics(p<0.05 for all).And this experiment also showed that the combining group of SC-560 and taxol had a synergistic influence on cyclin D1 expression compared with taxol group(p<0.05).While the expression of cyclin D1 in xenograft tumors of nude mice treated with SC-560 or SC-560 combined with DDP demonstrated no significant difference.In the SC-560,taxol,DDP,SC-560/taxol and SC-560/DDP groups,the Ki-67-positive cell index were 12.00%±3.22%,7.00%±2.27%,17.00%±1.68%,5.00± 1.32%,15.00 ± 2.12%,respectively,which was significant statistically in comparison with the level of the control group(29.00%±4.29%,p<0.05 for all).And we found that the combining group of SC-560 and taxol showed a synergistic influence on Ki-67-positive cells in comparison with the single medication group of taxol(p<0.05),but the combination of SC-560 and DDP didn't have the synergistic effect compared with the single medication group of DDP.Conclusion:This study shows that down-regulated cyclin D1 expression and cell proliferation were statistically significant,while the apoptotic index was notably increased in the drug-treated groups.These findings suggest that the combined treatment group of SC-560 and taxol has a synergistic impact on suppressing cyclin D1 expression,cell proliferation and promoting cell apoptosis in human ovarian cancer xenografts.