摘要
目的 观察微囊化CHO/pcDNA3.1/mIL 12细胞皮下移植及联合 5 FU对荷瘤小鼠的治疗作用。方法 将微囊化的CHO/pcDNA3 1/mIL 12细胞移植到荷瘤小鼠的皮下 ,观察肿瘤的生长速度、荷瘤小鼠的生存期 ,2 0d后 ,检测小鼠血清Th1和Th2类细胞因子IFN γ、IL 2、IL 12和IL 4、IL 10的水平及NK细胞和CTL细胞的活性。结果 经微囊化CHO/pcDNA3 1/mIL 12细胞皮下移植干预治疗后 ,小鼠血清Th1细胞因子水平明显升高 ,NK细胞和CTL细胞的活性明显增强 ,而Th2类细胞因子则明显降低 ;小鼠肿瘤的生长速度明显减慢 ,生存期明显延长 ;同时可部分改善化疗引起的免疫抑制作用。结论 微囊化的CHO/pcDNA3 1/mIL 12细胞皮下移植可以明显改善荷瘤小鼠的细胞免疫功能 ,部分减轻化疗引起的免疫抑制作用 ,对减慢肿瘤的生长速度和延长荷瘤小鼠的生存期均有明显的效果。
Objective To investigate the effect of subcutaneous transplantation of microencapsulated Chinese hamster ovary cells (CHO)/pcDNA3.1/mIL 12 and subcutaneous transplantation of microencapsulated CHO/pcDNA3.1/mIL 12 combined with 5 fluoro uracilum (5 FU) in treatment of tumor burdened mice. Methods CHO/pcDNA3.1/mIL 12 and CHO/pcDNA3.1 were suspended in solution of sodium alginate and made into microcapsules. Sixty mice were divided into 6 groups of 10 mice: (1) IL 12 group, microencapsulated CHO/pcDNA3.1/mIL 12 was injected subcutaneously, (2) combined treatment group: CHO/pcDN with 5 FU, (3) 5 FU group: 5 FU was injected intraperitoneally, (4) blank vector group: CHO/pcDNA3.1 was injected subcutaneously, (5) tumor burdened group: without any treatment, and (6) blank control group: normal mice without any treatment. Except the mice of the blank control group, all mice were injected subcutaneously into the inner side of right thigh with mice colonic adenoma cells. The volume of tumor was measured every third day. 20 days after the treatment, 5 mice in each group were killed to examine the serum Th1 type cytokines: interferon (IFN) γ, IL 12, and Th2 type cytokins: IL 4, IL 10 by double antibody sandwich ELISA. The spleens were made into suspension of lymphocytes to examine the activity of natural killer cell (NK) and cytolytic T lymphocyte (CTL). The survival period of the remaining 5 mice in each group was observed till the 60th day. Results The activity of NK and CTL were significantly much more in the IL 12 group than in other groups. The activity of NK was significantly much more in combined treatment group than in the tumor burdened group. The levels of Th1 type cytokines were the lowest in the tumor burdened group. There was no difference in the levels of Th1 type cytokine between the tumor burdened group and 5 FU group. However, the levels of Th1 type cytokine were significantly higher in the IL 12 group than in other groups. The levels of Th2 type cytokines were rather high in the tumor burdened group. There was no difference in the levels of Th2 type cytokine between the tumor burdened group and 5 FU group. However, the levels of Th2 type cytokine were the lowest in the IL 12 group than in other groups. There was no significant difference in volume of tumor among the tumor burdened group, blank vector group, and 5 FU group. The mean diameters of tumor in the IL 12 group and combined treatment group were significantly smaller than in the 5 FU, tumor burdened, and blank vector groups ( P <0.05), however, without a difference between the IL 12 group and combined treatment group. The survival periods of the IL 12 group and combined treatment group were significantly longer than those in the blank vector, tumor burdened and 5 FU groups ( P <0.05). Conclusion Microencapsulated CHO/pcDNA3.1/mIL 12 transplanted subcutaneously significantly improves the immune function of tumor burdened mice and partially overcomes immune suppression caused by chemotherapy, and is effective in slowing the growth of tumor and lengthening the survival period of tumor burdened ice.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2003年第1期51-54,共4页
National Medical Journal of China
