Effects Of Cyclooxygenase Inhibitors On Survival Time In Xenograft-bearing Ovarian Cancer Mice

Objective:The potent chemopreventive strategy for cancer which used cyclooxygenase (COX) inhibitors was thought to be a promising therapeutic target, but the capacity of the COX inhibitors (coxibs) in antitumor activity against ovarian cancer is still in dispute. The present study was designed to investigate whether coxibs could prolong the survival time by attenuating tumor growth of the xenograft-bearing ovarian cancer mice.Methods:Tumor growth and survival time were compared in mice which were xenografted with human ovarian SKOV-3carcinoma cells and treated with3mg/kg SC-560(a COX-1selective inhibitor) alone,25mg/kg Celecoxib (a COX-2selective inhibitor) alone, or SC-560/Celecoxib by gavage, every other day for a21days period from the day of tumor formed. The trail time was121days. To test the mechanism of inhibition of tumor growth by COX selective inhibitors, the mRNA and protein of COX-1and COX-2were determined by RT-PCR and Western blotting. The index of proliferating cells in tumor tissues was determined by immunostaining and the index of apoptotic cells by the terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.Resultes:In combination therapy of Celecoxib and SC-560, tumor volumes were significantly reduced compared with that of control group during the period after treated for14days (p<0.001), and the inhibitory rate on tumor growth in combination group was35.54%which is significant statistically compared with that of the control group (p<0.05). In the combination group, the index of cell proliferation and apoptosis were12.40%and51.03%respectively, which are significant statistically compared with those of the control group (22.56%,19.07%, all p<0.05). Single treatment of SC-560or Celecoxib significantly prolonged the mean survival time of mice compared with control group (p<0.05).Conclusions:Both COX-1and COX-2inhibitors could improve survival and inhibit tumor growth. And tumor growth inhibited by coxibs possibly contributes to the prolonged survival time in mouse xenograft model. These studies indicate that coxibs have particular potential for chemoprevention of ovarian cancer growth.