局部应用IL-12对小鼠S180实体瘤的抗瘤效应及机制初探

Antitumor Effects on Mice with S180 Solid Tumor Treated by Topical IL-12 and Its Mechanism

目的研究白细胞介素-12(Interleukin 12,IL-12)对小鼠S180实体瘤的抗肿瘤作用并初步探讨其机制.方法将小鼠左后肢皮下接种S180细胞荷瘤后的BaLB/c小鼠随机分为生理盐水组和IL-12组,分别给予生理盐水和IL-12.接种第28天,眼球取血,流式细胞仪分析外周血T细胞亚群的变化;解剖取瘤称重,计算瘤指数和抑瘤率,组织切片进行形态学观察.结果在接种瘤细胞第14天时,IL-12组、生理盐水组的肿瘤大小分别达到(7.56±0.09)mm、(8.52±0.46)mm,到第27天时,IL-12组的肿瘤大小为(5.12±1.56)mm,明显小于生理盐水组(15.34±3.18)mm(P<0.01).IL-12组的抑瘤率为(31.85±7.24)%,IL-12组的小鼠瘤指数为(5.51±1.35),与生理盐水组(7.67±0.67)相比差异具有显著性(P<0.01).IL-12组的小鼠血液中CD3+T、CD4+T、CD8+T细胞均高于生理盐水组.生理盐水组小鼠肿瘤细胞无明显坏死,并可见有丝分裂象,IL-12组的小鼠肿瘤组织有明显坏死,核固缩、细胞碎片多,但在瘤细胞之间很少见到淋巴细胞及巨噬细胞.结论 IL-12具有明显的抗肿瘤作用,初步显示涉及改变细胞亚群和诱导细胞凋亡的机制.

Objectives To study the antitumor function and mechanism of IL-12 in treating S180 solid tumors in mice.Methods The tumor-bearing mice which were inoculated with S180 cells（1×107/ml） subcutaneously in the left hind limb were divided into two groups：NS control group and IL-12 treatment group.And NS,IL-12 were respectively given to the mice of two groups.The ocular blood was removed from the mouse of each group on the 28th day to analyze.Then CD3＋T,CD4＋T,CD8＋T and the ratio of CD4/CD8 of peripheral blood was analyzed with FCM,and tumor tissue was dissected completely for weighting and calculating the inhibition rate and index.The regular diet and physical conditions of the remaining mice were observed,and their tumor size was measured.Results On the 14th day,tumor size of NS control group,IL-12 group respectively got to（8.52±0.46） mm,（7.56±0.09） mm.Then it began to reduce in the IL-12 group.On the 27th day,tumor size was（5.12±1.56） mm and significantly less than that of NS control group（15.34±3.18） mm（P0.01）.The tumor inhibition rate of IL-12 group was（31.85±7.24）%,significantly higher than that of NS group（P0.01）.Tumor index of NS control group was 7.67 ± 0.67 and tumor index of IL-12 group was 5.51±1.35,which was significantly lower than that of NS control group（P0.01）.CD3＋T,CD4＋T,CD8＋T cells in mice blood of IL-12 group were all higher than that of NS control group.Tumor cells of mice in NS group had no significant necrosis,and Mitosis was observed.Tumor tissue of mice in IL-12 group had significant necrosis with most karyopyknosis and cell debris,but lymphocytes and macrophages between tumor cells rarely seen. Conclusions IL-12 has apparente effects in anti-tumor immune response.And it demonstrats that IL-12 relates to the mechanism of changing cell subpopulation and leading apotosis.