Inhibition effect to colorectal cancer induced by synergistic usage of celecoxib and 5-FU and its mechanism

OBJECTIVE:To research the anti-tumor effect and investigate its mechanisms of 5-FU combined with celecoxib on the treatment of human colon cancer implantation in BALB/C nude mice.METHODS: The treatment effects of 5-FU combined with celecoxib were observed in nude mice subcutaneously transplanted human colon cancer induced by Lovo cell.Immunohistochemistry and western blot were selected for estimating the expression of Cox-2,Caspase-3,Caspase-9 and Cytochrome C.Transmission electronic microscope was used to observe the apoptosis morphous and TUNEL was used to detect the apoptosis of cancer cell and determine apoptotic index.RESULTS:The effect of combined application of celecoxib and 5-FU was better than that of other groups.The rate of the tumor inhibition of B group,C group and D group were 16.93%,56.16%,77.06%,and the statistical difference compared with control group(0)was obvious(P0.01).Compared with control group,the apoptosis in treated groups conspicuously increased and the statistical differences of the apoptotic index among treated groups were obvious(P0.01).The results of western blot and immunohistochemistry displayed that the expression of Caspase-9,Caspase-3 and Cytochrome C of treated groups raised obviously compared with the control group.Contemporaneously,the statistical differences of the expression of Caspase-9,Caspase-3 and Cytochrome C in the treatment groups were also remarkable(P0.05).The expression of Cox-2 of C group and D group decreased evidently compared with control group and B group.The expression of Cox-2 of D group was minimum.CONCLUSIONS:5-FU combined with celecoxib obviously inhibited the growth of human colorectal cancer in nude mice subcutaneous xenograft.The mechanism of antitumor may be correlated with reciprocal hypersensitivity and inducing apoptosis and activation mitochondrion accommodation pathway by upregulating the expression of Caspase-9,Caspase-3 and Cytochrome C.