循环应用低剂量环磷酰胺联合白细胞介素-2对乳腺癌荷瘤小鼠调节性T细胞及生存期影响

Influence of Cyclical Administration with Low-dose Cyclophosphamide and Interleukin-2 on Regulatory T Cells of Murin Breast Cancer Model and Its Life Span

目的了解循环应用小剂量环磷酰胺(CTX)联合白细胞介素-2(IL-2)对4T1Balb/c乳腺癌荷瘤小鼠调节性T细胞(Treg)及其生存期影响。方法通过皮下接种4T1乳腺癌细胞建立乳腺癌Balb/c荷瘤小鼠模型;荷瘤小鼠随机分为IL-2组、CTX组、IL-2+CTX组及对照组,在种瘤第10天开始对荷瘤小鼠分别经腹腔按方案给药,部分小鼠在末次给药后4天处死,流式细胞术检测小鼠脾脏中CD4+CD25+/CD4+调节性T细胞数量;余小鼠观察生存期。结果 IL-2组、CTX组、IL-2+CTX组及对照组调节性T细胞比例分别为26.00%±0.98%、11.30%±0.85%、20.15%±1.11%、17.50%±1.13%,组别之间差异均有显著性(P<0.05)。IL-2+CTX组小鼠最长存活57天,对照组小鼠最长存活46天,差异具有显著性(P<0.05)。结论 IL-2联合循环应用CTX将调节性T细胞持续维持在较低水平,从而延长小鼠生存期。

Objective To observe the influence of cyclical administration with Cyclophosphamide （CTX） and Inter- leukin-2 （IL-2） on regulatory T cells （Treg） of murine breast cancer model and its life span. Methods Murine breast cancer model was established by inoculating s. c. mice with 4T1 breast cancer tumor cell line. Tumor-bearing BALB/c mice were randomly divided into four groups ： IL-2 group and CTX group and IL-2 ＋ CTX group and control group. Mice in groups were injected intraperitoneally on schedule at the tenth day after tumor was established. Part of mice were sacrificed on day 4 after the last adminstration. We examined Regulatory T ceils ratio of spleen cells by flow cytometry. Others were observed for survival. Results The CD4 ＋ CD25 ＋/CD4＋ ration in spleens of IL-2 group, CTX group, IL-2 ＋ CTX group and con- trol group were 26.00%± 0.98%, 11.30% ±0.85% ,20. 15% ± 1. 11%, 17.50% ± 1. 13% respectively. Significant differences were observed between each group（ P 〈 0.05 ）. The longest life span in IL-2 ＋ CTX group and control group were 57 days and 46 days respectively, significant differences were observed between these groups. Conclusions Cyclical ad- ministration of low dose CTX keep Treg ratio which were expanded by IL-2 in a low level lead to a longer life span.