The Study Of The Effect Of Epirubicin Combined With Celecoxib On Skbr-3Cell And Breast Cancer-Bearing Nude Mouse Models

Objective:To approach the effect of Epirubicin combined with Celecoxib on SKBR-3cell and breast cancer-bearing nude mouse models,the activition of expression of Caspase-3, the inhibition of expression of VEGF and COX-2, and its mechanism on anti-breast cancer.Methods:In vitro, SKBR-3cells being stimulated by different concentration of Epirubicin and Celecoxib, CCK-8assay was adopted to examine the inhibition of cell proliferation. Flow cytometry was performed to analyze the cell cycle of SKBR-3. Western Blot was used to detect the activation of Caspase-3. In vivo, in order to establish tumor model, SKBR-3cells were intracutaneously injected on nude mouse armpit. After that,36Balb/c breast cancer-bearing nude mice were randomized into6groups; Group A:normal saline(0.2ml/mouse only).Group B:Epirubicin group (Epirubicin1.8mg/kg). Group C:Epirubicin group(3.6mg/kg). Group D:Celecoxib group(Celecoxib40mg/kg). Group E:Celecoxib combined high-dose of Epirubicin group(Celecoxib40mg/kg+Epirubicin 3.6mg/kg).Group F:Celecoxib combined low-dose of Epirubicin group (Celecoxib40mg/kg+Epirubicin1.8mg/kg). When tumor’s diameter reached3-5mm, all drugs were administrated. Celecoxib were injected into peritoneal cavity every day sustained six days, but Epirubicin in vein. The nude mice were weighted and the volume of tumors was measured every three days. Every nude mouse was sacrificed at the21th day after drug administration. Specimens of tumor were collected to observe the effect of the different medicines on the tumor body weight, volume and inhibition rate. The expression of VEGF and COX-2were detected by immunohistochemical staining.Results:In vitro, Celecoxib and Epirubicin obviously inhibited the proliferation of SKBR-3cells in time-and dose-dependent effects. With the increase of doses of Epirubicin and Celecoxib, the cell cycle was arrested at G0/G1, and rate of cells in S-phase was obviously decreased. Caspase-3was activated in the early stage of apoptosis, but there was no expression in the late period of apoptosis. In breast cancer-bearing nude mouse, Epirubicin combined with Celecoxib inhibited growth of tumor, and also increased the inhibition rate. Compared to Group A, each group had significant treatment effect(P<0.05). The body weight of tumor was lightest in Group A had. Compared with Group A, the tumor volume in each dose group had significant difference(P<0.05). The VEGF expression was significantly inhibited by high-dose Epirubicin(P<0.05); so was the COX-2, but by Celecoxib(P<0.05). The two drugs could inhibit the VEGF, COX-2expression(P<0.05).Conclusion:Epirubicin and Celecoxib can inhibit the proliferation of SKBR-3cells, and induce apoptosis. In breast cancer-bearing nude mouse models, Epirubicin combined with Celecoxib inhibit the growth of tumor, and the combination of two drugs significantly increase the inhibition rate, and reduce the expression of VEGF and COX-2. Their mechanism of action may be associated with inhibition of activation of Caspase-3, and the depress of expression of VEGF and COX-2.