The Antitumor Effect And Mechanism Of Celecoxib In Human Nasopharyngeal Carcinoma Xenografts

ObjectiveTo investigate whether celecoxib, a selective of cyclooxygenase-2 inhibitors, can exert antitumor effect in human nasopharyngeal carcinoma xenografts. At the same time, the possible mechanisms of these effects were also investigated.MethodsThe cyclooxygenase-2 level of CNE1 cell line (derived from human nasopharyngeal carcinoma) was detected by immunohistochemistry. After treatment with celecoxib,the inhibitory effects of celecoxib on the proliferation of cancer cells were quantified by MTT assay .Suspensions of CNE1 cells were injected s.c. into the right thighs of BALB/C female nude mice to make xenografts. The mice bearing tumors were divided into two groups randomly: the control group, the group with celecoxib.Each group consisted of 8 mice. The mice were treated with celecoxib 4 days after transpiantation. Tumor volume and weight were measured. The time was observed that all tumors grew from 6mm to 16mm in the longest diameters; Calculate the tumor growth delay and draw the tumor growth curves. The mice were killed when the longest diameters of tumors got 16mm. Then the tumor tissues were taken out to detect the expression level of COX-2.vascular endotheliaI growth factor (VEGF) , survivin detected by immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR). Results1. Cyclooxygenase-2 protein was detected in CNE1 cell lines.2. Celecoxib inhibited the proliferation of the tumor cells in time and dose-dependent manners.3. Celecoxib prolonged significantly the time that the tumors grew from 6mm to 16mm in the longest diameter. The time were 54.63±7.11 days in the group with celecoxib alone and 45.25±7.80 days in the control group, respectively (P=0.025).4. The expression levels of COX-2,VEGF,survivin detected by immunohistochemistry.were significantly lower in celecoxib group than in controI group (3.25±1.28 vs 4.50±0.93, 2.88±1.13 vs 4.63±1.06, 3.13±1.13 vs 5.13±1.13 P<0 05,respectively).5. The expression levels of COX-2,VEGF,survivin detected by RT-PCR.were significantly lower in celecoxib group than in controI group (0.17±0.05 vs 0.28±0.09, 0.15±0.05 vs 0.23±0.05, 0.30±0.08 vs 0.42±0.06, P<0 05,respectively)Conclusion1. Celecoxib can exert antitumor effect in human nasopharyngeal carcinoma CNE1 cell and xenografts.2. Celecoxib has inhibitory effects on nasopharyngeal carcinoma.The activity of COX-2 which is inhibited by celecoxib is probably related to the production of VEGF and survivin modulated by COX-2.