白细胞介素-2联合环磷酰胺对乳腺癌荷瘤小鼠调节性T细胞的影响  

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

作　　者：佘键涛[1] 康颖[2] 刘红光[1] 田绍文[3] 刘登辉[1] 文波[1] 赵茂勋[1] 王雄宇[1] 

机构地区：[1]南华大学附属第一医院肿瘤防治中心,湖南衡阳421000 [2]南华大学医学院外科教研室,湖南衡阳421000 [3]南华大学医学院生理教研室,湖南衡阳421000

出　　处：《现代生物医学进展》2013年第14期2636-2639,2685,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30770689);湖南省卫生厅科研计划课题项目(B2010-039)

摘　　要：目的:调节性T细胞(Regulatory T cells,Treg)被认为能够抑制抗肿瘤免疫反应,从而促进肿瘤生长。环磷酰胺(Cyclophosphamide,CTX)是个常规化疗药物,现在更多的注意力集中在其小剂量应用时可以删除Treg。了解小剂量环磷酰胺联合白细胞介素-2(Interleukin-2,IL-2)对4T1Balb/c乳腺癌荷瘤小鼠调节性T细胞的影响及其抗肿瘤效果。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;20只荷瘤小鼠随机分为IL-2+NS组、PBS+CTX组、IL-2+CTX组及PBS+NS组,在种瘤第10天开始对荷瘤小鼠分别经腹腔按方案给药。在种瘤后第16天人道处死小鼠,采用流式细胞术检测小鼠脾脏中CD4+CD25+调节性T细胞数量,应用ELISA法检测血清干扰素-γ浓度,电子称称量肿瘤重量。结果:与对照组相比,在应用IL-2后,荷瘤小鼠脾脏CD4+CD25+/CD4+比值增加,在应用IL-2的同时使用小剂量CTX可减少CD4+CD25+/CD4+的比值;单次及联合用药均可提高血清INF-γ浓度;联合用药可减少肿瘤重量。结论:小剂量CTX可以减少由使用IL-2所增加的Treg数量,促进抗肿瘤免疫,提高IL-2的抗瘤效果,从而抑制肿瘤生长。该研究可能为乳腺癌的临床治疗提供一种有效的方法。Objective： Regulator T cells are thought to facilitate tumor development by suppressing antitumor immune responses.Cyclophosphamide is a conventional drug used in chemotherapeutics,and now much attention is focused on the Treg depletion of low dose CTX.To observe the influence of administration with Interleukin-2（IL-2） and Cyclophosphamide（CTX） on Regulatory T cells（Treg） of murine breast cancer model and its antitumor effect.Methods： Murine breast cancer model were established by inoculating s.c.mice with 4T1 breast cancer tumor cell line.Twenty BALB/c mice were randomly divided into four groups： IL-2＋NS group,PBS＋CTX group,IL-2＋CTX group and PBS＋NS group.Mice in groups were injected intraperitoneally on schedule at the tenth day after tumor has been established.Mice were sacrificed at the sixteenth day.We examined Regulatory T cell（Treg） ratio of spleen cells by flow cytometry.INF-λ concentration was measured using ELISA kit.Tumor weight was measured using a electronic scale.Results： Administration with IL-2 increased the CD4＋CD25＋/CD4＋ ration in spleens compared to control group.Low dose CTX could reduce the CD4＋CD25＋/CD4＋ratio which were augmented by IL-2.Administration with IL-2,CTX and both of them increased serum INF-λ concentration.Furthermore,administration with low dose CTX and IL-2 effectively reduced tumor weight in tumor-bearing mice.Conclusion： Administration with low dose CTX could reduce the number of Treg which were augmented by IL-2 and promote anti-tumor immune response.This enhances the anti-tumor effect of IL-2 and suppresses tumor growth.This study provides a possible methed for breast cancer clinical therapy.

关 键 词：环磷酰胺 调节性T细胞 白细胞介素-2 肿瘤免疫 

分 类 号：Q95-3[生物学—动物学] R737.9[医药卫生—肿瘤]