Effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer xenografts in nude mice

Objective To evaluate the effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer (TNBC) xenografts in nude mice.Methods Human TNBC MDA-MB-231 cells were inoculated subcutaneously into BALB/c nude mice.The mice (n=32) were then randomly divided into 4 groups,the control group and the celecoxib group (receiving 25,50,100 mg·kg-1·d-1 respectively).At the end of the study,tumor tissues were collected and tumor volume was measured.Cell apoptosis was determined by flow cytometry (FCM) analysis.NF-κB p65 and pS0 protein levels were measured by immunohistochemistry.Caspase-3 and survivin protein levels were detected by western blotting.Results celecoxib at dose of 25,50 and 100 mg·kg-1·d-1 inhibited the tumor growth significantly,compared with the control group.FCM results showed that apoptotic rates were (13.58±3.16) ％ and (21.91±4.75) ％ in moderate and high dose of celecoxib-treated group,compared with (3.15±1.73) ％ in control group (t =6.736,P ＜ 0.05;t =12.151,P ＜ 0.05).p65 expressions were 79.3 ％,46.7 ％ and 23.9 ％ in low,moderate and high dose of celecoxib-treated group,compared with 89.7 ％ in control group (x2 =3.312,P ＜ 0.05; x2 =10.785,P ＜ 0.05;x2 =15.900,P ＜ 0.05).Besides,western blotting analysis demonstrated that celecoxib significantly downregulated survivin expression,while upregulated the active form of caspase-3 expression.Conclusion Celecoxib could suppress TNBC tumor growth and induce cell apoptosis,which might be partially associated with inactivation of p65 and downregulation of survivin. Key words: Celecoxib;  Breast neoplasms;  Apoptosis;  NF-κB;  Animal experimentation