Study On Effect And Mechanism By Synergistic Usage Of Celecoxib And 5-FU For The Treatment Of Human Colorectal Cancer (HCC) In BALB/C Nude Mice Subcutaneous Xenograft Model

Objective To investigate the anti-tumor effect and explore its mechanisms of celecoxib(a selective cox-2 inhibitor) combined with 5-Fluorouracil(5-FU) on the treatment of human colorectal cancer in BALB/C nude mice subcutaneous xenograft model .Methods The cell line HT-29 in log phase of human colorectal cancer was implanted subcutaneously in BALB/C nude mice to develop implant-tumor,and subcutaneously implanted tumor 1 weeks later.Then 32 nude mice were randomly allocated into four groups. After treating with 5-FU or (and) celecoxib ,the tumor growth in mice were observed.The volume and weight of implant-tumor were measured and the rates of cancer inhibition were evaluated.Simultaneously the method of immunohistochemistry and western blot were used to estimate the expression of Cytochrome C,caspase-3 and caspase-9,the apoptosis morphous was detected by fluorescence microscope and electron microscope and the apoptosis of tumor cell was detected by TUNEL to determine apoptotic index (AI).Results None of the nude mice died and all nud mice formed implant-tumor.The effect of synergistic usage of 5-FU and celecoxib for the treatment of human colorectal cancer was better than other groups.The respective rates of the tumor inhibition of B group,C group and D group were 27.81%,53.02%,78.37%,and the differences compared with control group (0%)were significant(P<0.01).Compared with control group the apoptosis of tumor cell in treated groups notably raised and the statistical differences of the apoptotic index(AI) among treated groups were significant(P<0.01).The means of fimmunohistochemistry and western blot display that the expression of Cytochrome C,caspase-3 and caspase-9 of treated groups increased obviously compared with the control group.Meanwhile the statistical differences of the expression of Cytochrome C,caspase-3 and caspase-9 among the treated groups were also significant(P<0.05). Conclusions Celecoxib and 5-FU have respective effect to inhibit the growth of tumor.Compared with celecoxib or 5-FU individual drug group, Celecoxib combined with 5-FU significantly inhibited the growth of human colorectal cancer in nude mice subcutaneous xenograft. The mechanism of antitumor maybe is correlate with inducing apoptosis and activation mitochondrion accommodation pathway by upregulating the expression of Cytochrome C,caspase-3 and caspase-9.