The Effect And Mechanism Of Genetically Engineered Salmonella Overexpressing Flagellin On Two Mouse Colon Cancer Models

Objective:To investigate the effect of genetically engineered Salmonella with flagellin overexpression on BALB / c and C57 BL / 6 mouse colon cancer models and the mechanism of immune cytokines in tumors.Methods: Fifteen BALB / c and Fifteen C57 BL / 6 mice were selected to establish subcutaneous colon cancer models in BALB / c and C57 BL / 6 mice.BALB / c mice were divided into Fla B positive treatment group(n = 5),Fla B negative treatment group(n = 5)and control group(n = 5),and C57BL/6 mice were divided into the same groups as BALB/c mice.When the tumor size reached about 150 mm3,genetic engineering bacteria were injected to continuously observe the mouse modeling and monitor the tumor volume.Arabinose liquid was injected intraperitoneally on the 3rd day after injection.On the 5th day after injection,the level of cytokine infiltration in tumor tissues of mice was detected by bead multiplex immunoassay,including pro-inflammatory or anti-inflammatory cytokines,colony stimulating factors and chemokines.Result:(1)C57BL / 6 mice : The expression levels of IL-10 and CXCL5 in tumor tissues of Fla B positive treatment group were significantly higher than those of Fla B negative treatment group and PBS control group,while the expression levels of IFN-γand TNF-α were significantly higher than those of PBS control group,but lower than those of Fla B positive treatment group.The expression levels of the above cytokines were statistically significant(P < 0.05).(2)BALB / c mice : The expression levels of IL-1α and CXCL5 in tumor tissues of Fla B positive treatment group were significantly higher than those in Fla B negative treatment group and PBS control group,while the expression levels of IL-5 and IL-17 A were significantly higher than those in PBS control group,but lower than those in Fla B positive treatment group.The expression of IL-7 in Fla B positive treatment group and Fla B negative treatment group was significantly lower than that in PBS control group.Among them,the expression level of TNF-α in the Fla B negative treatment group was significantly higher than that in the PBS control group,and the difference in the expression level of the above cytokines was statistically significant(P < 0.05).There was no significant difference in the expression levels of other cytokines(IL-1β,IL-2,IL-4,IL-6,IL-10,IL-12(p70),IL-13,MCP-1 and GM-CSF)among the groups of C57 BL / 6 mice(P > 0.05).Conclusion:(1)Attenuated Salmonella carrying Fla B recombinant plasmid significantly inhibited the growth of colorectal cancer in C57 BL / 6 mice and transiently inhibited the growth of colorectal cancer in Balb / C mice.(2)Cytokines IL-7 and IL-10 may have a positive regulatory role in anti-tumor immunity,while TNF-α may weaken the anti-tumor immune response,and CXCL5 may be associated with adverse prognosis.