Effects And Mechanism Of Juglone In Combination With 5-FU On CT-26 Colon Cancer Cells In Vivo

In order to exploit the inhibition effect and mechanism of Juglone itself or combinated with 5-FU in mouse colon cancer CT-26 cells in vivo and improvement effect of Juglone on toxic site effect caused by 5-FU, such as myelosuppression and reduction of immune organ index.Construct mouse model transplanted with colon cancer CT-26 cells, randomly divided into 6 groups, model group, positive drup group(20.0mg/kg 5-FU), Juglone low-dose group(2.5mg/kg), Juglone large-dose group(5mg/kg), combination low-dose group(5mg/kg Juglone +10mg/kg 5-FU), combination large-dose group(5mg/kg Juglone +20mg/kg 5-FU). After 9 days of continuous administration, animal treatment and sample collection were carried out. Detection index included morphological observation of HE staining, thymus index, spleen index, VEGF, IL-2, TNF-α, IFN-γand immunohistochemical test results of Ki-67, E-cad, P53, Bcl-2.The inhibition rates of the Juglone high and low-dose group were 40.38% and 31.73%, respectively, and the combination high and low-dose group were 75.01% and 56.73%. Compared with the model group, each treatment group can significantly increase the expression of IL-2, TNF-αand IFN-γ. The results of immunohistochemistry showed that juglone alone and combination ofjuglone and 5-FU could significantly reduce expression of Ki-67 and Bcl-2 genes and enhance the expression of E-cad gene associated with cell adhesion.In summary, Juglone has a clear inhibitory effect on the growth of colon cancer CT-26 cells in mice, and this effect is dose dependent, and can inhibit angiogenesis, enhance cell viscosity, reduce the risk of tumor cell metastasis and proliferation. Meanwhile, Juglone can increase cell adhesion in order to reduce the risk of tumor cell metastaisis. Juglone can enhance the function of the immune system of the body. The possible anti-tumor mechanism of Juglone is down regulating the expression of Bcl-2 gene, one of tumor suppressor genes, to induce the apoptosis of tumor cells. Anti-tumor effect of combination of Juglone and 5-FU is synergistic enhancement and Jugone can clearly improve toxic site effect caused by 5-FU, such as myelosuppression and reduction of immune organ index.