Anti-Foxp3dsFv-IL-6融合蛋白干预Treg/Th17失衡抑制结肠癌细胞分化的初步研究

A preliminary study on the intervention of anti-Foxp3dsFv-IL-6 fusion protein in Treg/Th17 imbalance to inhibit the differentiation of colon cancer cells

目的观察anti-Foxp3dsFv-IL-6融合蛋白干预Treg/Th17失衡从而抑制结肠癌细胞分化的效果。方法清洁级雌性BALB/c小鼠分为3组,每组12只。均于小鼠后背皮下接种结肠癌细胞株CT26。1周后A组小鼠给予注射anti-Foxp3ds Fv-IL-6融合蛋白,B组小鼠给予注射PBS,C组小鼠不做处理。检测各组小鼠在接种结肠癌细胞株CT26初期、注射anti-Foxp3ds Fv-IL-6融合蛋白或PBS时、注射后1周3个时间点体内Treg/Th17的状态;并观察各组小鼠的生存期。结果 A组小鼠给予注射anti-Foxp3ds Fv-IL-6融合蛋白后,Treg下降而Th17上升,Treg/Th17比值降低(由3.77降至0.92);而B组小鼠和C组小鼠的Treg/Th17比值升高(分别由3.69升至3.96、由3.80升至3.88)。A组、B组和C组小鼠的存活时间分别为(24.9±2.7)d、(16.4±1.8)d、(16.8±1.5)d。单向方差分析提示组间差异有统计学意义(P<0.05);LSD检验提示A组与B组、A组与C组之间的差异均有统计学意义(P<0.05),B组与C组之间的差异无统计学意义(P>0.05)。结论 anti-Foxp3ds Fv-IL-6融合蛋白通过干预Treg/Th17失衡进而抑制结肠癌细胞的分化。

Objective To observe the effect of inhibition of the differentiation of colon cancer cells initiated by the interference of anti-Foxp3 ds Fv-IL-6 fusion protein on the imbalance of Treg/Th17. Methods Clean female BALB/c mice were divided into 3 groups. Each group was subcutaneously inoculated with colon cancer cell line CT26. After 1 week, the mice in group A were injected with anti-Foxp3 ds Fv-IL-6 fusion protein, and the mice in group B were injected with PBS, and the mice in group C were not treated. In vivo Treg/Th17 state were detected in each group of mice in the following three time points: in the initial stage when the colon cancer cell line was injected, when anti-Foxp3 ds FvIL-6 fusion protein or PBS was injected and 1 week after the injection. At the same time, the survival of each group of mice were observed. Results In group A, after the mice were injected with antiFoxp3 ds Fv-IL-6 fusion protein, the proportion of Treg decreased and the proportion of Th17 cells increased, and the ratio of Treg/Th17 decreased. While in group B and group C, the ratio of Treg/Th17 increased. The survival time of group A, group B and group C were(24.9±2.7) d,(16.4±1.8) d and(16.8±1.5) d, respectively. Analysis of One-Way ANOVA suggested that there was significant difference between the groups(P<0.05); There was significant differences between the group A and group B(P<0.05), while there was no significant difference between group B and group C(P>0.05). Conclusion AntiFoxp3 ds Fv-IL-6 fusion protein can inhibit the differentiation of colon cancer cells by interfering with the imbalance of Treg/Th17.