L-精氨酸促进乳腺癌荷瘤小鼠T细胞应答

L-arginine promotes T cell mediated immune response in mice with breast cancer

目的探讨L-精氨酸(L-Arg)对乳腺癌的治疗效果及相关机制。方法制备4T1小鼠乳腺癌荷瘤模型,实验组小鼠于成瘤后连续给予灌胃L-Arg(1.5 g/kg)20 d。动态监测肿瘤组织大小和生存率,处理结束时处死小鼠,制备脾细胞悬液,经流式细胞术检测T细胞亚群和巨噬细胞比例,ELISA检测脾细胞培养上清IFN-γ和TNF-α水平,Griess反应测定上清中NO含量。结果与对照组相比,L-Arg处理可以抑制肿瘤的生长,延长小鼠生存期;同时,L-Arg处理组中脾细胞中CD4+T(26.53±4.25)%、CD8+T细胞(15.65±0.78)%和巨噬细胞(7.62±0.86)%比例明显高于PBS组[分别为(19.53±2.50)%、(8.78±1.15)%和(2.02±0.12)%],脾细胞培养上清中IFN-γ(36.56±10.50)pg/mL、TNF-α(22.05±4.93)pg/mL和NO(30.28±6.00)μm的分泌水平也明显高于PBS组[(分别为(15.47±4.96)pg/mL、(14.69±0.81)pg/mL和(6.57±2.21)μM]。结论 L-Arg可通过促进乳腺癌荷瘤小鼠的T细胞应答,发挥抗肿瘤效应。

Objective To explore the role of L-arginine （L-Arg）in the treatment of breast cancer.Methods The experimental rodent model of breast cancer was prepared by injecting 4T1 cell line into the right side body of the mouse.The mice in L-Arg group were orally treated with L-Arg（1.5 g/kg）for successive 20 days when the tumor could be detected with palpation.Tumor size and survival rate were dynamically monitored.The mice were sacrificed and the spleen cell suspension was prepared when the treatment ended.Fluorescence activated cell sorter （FACS）was used to detect the T subsets and macrophage.Enzyme-linked immunosorbent assay（ELISA）and Griess reaction were used to detect interferon-gama（IFN-γ）,interferon-alpha （TNF-α）,and nittric oxide （NO）,respectively.Results Compared with the control,treatment with L-Arg could inhibit tumor growth,prolong survival time of the mice.Meanwhile,L-Arg treatment significantly increased the percentages of CD4＋ T（26.53±4.25%）,CD8＋ T cells（15.65±0.78%）and macrophages（7.62±0.86%） compared with the control group（19.53±2.50%,8.78±1.15%,and 2.02±0.12%,respectively） of the spleen cells.The contents of IFN-γ（36.56±10.50 pg/ml）,TNF-α（22.05±4.93 pg/ml） and NO（30.28±6.00 μM） levels in L-Arg group were also significantly higher than those of the control group（15.47±4.96 pg/ml,14.69±0.81 pg/ml,and 6.57±2.21 μM,respectively,in the spleen cell culture supernatant.Conclusion L-Arg enhances T cell mediated immune response against tumor in the mice with experimental breast cancer.