多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究

曹爱玲; 曹　喆; 周　剑

doi:10.19401/j.cnki.1007-3639.2021.09.005

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多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究

论著 | 更新时间：2025-12-31

- 多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究
- Effects of docetaxel combined with thymosin α1 on number of Treg in immune microenvironment of rats with breast cancer and its mechanism
- 中国癌症杂志 2021年31卷第9期页码：799-806
- 作者机构：
  
  咸宁市中心医院 / 湖北省科技学院第一临床医学院肿瘤科,湖北,咸宁,437000
- 作者简介：
- 基金信息：
  
  湖北省教育厅重点基金项目（D20152812）。
- DOI：10.19401/j.cnki.1007-3639.2021.09.005
  中图分类号：
- 网络出版：2021-10-08，
  
  纸质出版：2021-10-08
- 稿件说明：
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曹爱玲, 曹　喆, 周　剑. 多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究[J]. 中国癌症杂志, 2021, 31(9): 799-806.

曹爱玲, 曹　喆, 周　剑. Effects of docetaxel combined with thymosin α1 on number of Treg in immune microenvironment of rats with breast cancer and its mechanism[J]. China Oncology, 2021, 31(9): 799-806.
曹爱玲, 曹　喆, 周　剑. 多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究[J]. 中国癌症杂志, 2021, 31(9): 799-806. DOI： 10.19401/j.cnki.1007-3639.2021.09.005.

曹爱玲, 曹　喆, 周　剑. Effects of docetaxel combined with thymosin α1 on number of Treg in immune microenvironment of rats with breast cancer and its mechanism[J]. China Oncology, 2021, 31(9): 799-806. DOI： 10.19401/j.cnki.1007-3639.2021.09.005.

摘要

背景与目的：乳腺癌患者体内存在严重的免疫失衡，胸腺肽α1（thymosin α1，Tα1）作为免疫增强剂发挥作用，探究多西他赛（docetaxel，DCT）联合Tα1对大鼠乳腺癌免疫微环境中调节性T细胞（regulatory T cell，Treg）数量的影响，并初步分析其作用机制。方法：随机将60只雌性SD大鼠分为模型组、DCT组（剂量为10 mg/kg）、Tα1组（剂量为0.8 mg/kg）及3个DCT+Tα1组（DCT剂量为10 mg/kg，Tα1剂量分别为0.2、0.4、0.8 mg/kg），每组10只。给雌性SD大鼠接种大鼠乳腺癌细胞系SHZ-88建立移植瘤模型，成瘤后，DCT组、Tα1组及DCT+Tα1组分别腹腔注射相应剂量的DCT、Tα1，给药周期均为20 d，1次/d。测量大鼠肿瘤体积，采用原位末端转移酶标记（TdT-mediated dUTP nick end labeling，TUNEL）染色法检测肿瘤细胞的凋亡情况。采用流式细胞术检测大鼠肿瘤组织中CD4

＋

CD25

＋

Foxp3

＋

Treg数量及表达程序性死亡［蛋白］-1（programmed death-1，PD-1）的Treg数量，采用酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测肿瘤组织中白细胞介素-10（interleukin-10，IL-10）、转化生长因子-β（transforming growth factor-β，TGF-β）的表达，采用蛋白质印迹法（Western blot）检测肿瘤组织中PD-1及程序性死亡［蛋白］配体-1（programmed death ligand-1，PD-L1）的表达。结果：与模型组相比，给药组均可明显抑制肿瘤的生长，促进肿瘤细胞凋亡，显著下调CD4

＋

CD25

＋

Foxp3

＋

Treg数量，以及IL-10、TGF-β、PD-1和PD-L1的表达（P ＜ 0.05），其中DCT+0.8 mg/kg Tα1组作用效果最显著，明显优于其他给药组。结论：DCT联合Tα1可抑制大鼠肿瘤的生长，其中以DCT+0.8 mg/kg Tα1效果最显著，作用机制可能是通过下调PD-1/PD-L1的表达，抑制CD4

＋

CD25

＋

Foxp3

＋

Treg浸润。

Abstract

Background and purpose: There is severe immune imbalance in breast cancer patients. Thymosin α1 (Tα1) acts as an immune enhancer. The aim of this study was to explore the effects of docetaxel (DCT) combined with Tα1 on number of regulatory T cell (Treg) in immune microenvironment of rats with breast cancer

and preliminarily analyze its action mechanism. Methods: Sixty female SD rats were randomly divided into model group

DCT group (10 mg/kg)

Tα1 group (0.8 mg/kg) and three DCT+Tα1 (10 mg/kg DCT; 0.2

0.4

0.8 mg/kg Tα1) groups with 10 cases in each group. SD female rats were inoculated with breast cancer cell line SHZ-88 to construct xenograft models. After tumor formation

DCT group

Tα1 group and DCT+Tα1 group were given intraperitoneal injection of DCT and Tα1 respectively. The administration period was 20 d

once a day. The tumor volume was measured. TdT-mediated dUTP nick end labeling (TUNEL) staining was applied to detect apoptosis of tumor cells. The number of CD4

CD25

Foxp3

Treg

expression of programmed death-1 (PD-1) and number of Treg in tumor tissues were detected by flow cytometry. The expressions of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of PD-1 and programmed death ligand-1 (PD-L1) in tumor tissues were detected by Western blot. Results: Compared with model group

drug administration effectively inhibited tumor growth

promoted apoptosis of tumor cells and significantly down-regulated the number of CD4

CD25

Foxp3

Treg and expressions of IL-10

TGF-β

PD-1 and PD-L1 (P ＜ 0.05). The action effect in DCT+0.8 mg/kg Tα1 group was the most significant

which was significantly better compared with the other administration groups. Conclusion: DCT combined with Tα1 can inhibit growth of rat tumor. The effect of DCT+0.8 mg/kg Tα1 is the most significant

and its mechani

sm may involve down-regulating expression of PD-1/PD-L1 and inhibiting infiltration of CD4

CD25

Foxp3

Treg.

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