A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model
A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model
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DOI：
10.1016/j.intimp.2010.06.005
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发表时间：
2010-09-01
影响因子：
5.6
通讯作者：
Noori, Shokoofe
中科院分区：
文献类型：
--
作者：
Langroudi, Ladan;Hassan, Zuhir Muhammad;Noori, Shokoofe
背景：青蒿素（Artemisinin，ART）是一种倍半萜内酯。在抗疟药中，具有内过氧化物桥是独一无二的，现在人们的注意力都集中在ART的抗癌特性上。在这项研究中，我们的目的是将青蒿素在乳腺癌治疗中的免疫调节作用与常规抗癌药物环磷酰胺（CTX）进行比较。我们检查了迟发型超敏反应，抗体和IL-4和IFN γ的产生，肿瘤体积，肿瘤浸润的调节性T细胞（Treg）和脾淋巴细胞增殖试验。简言之，用2.8 mg/kg ART和20 mg/kg CTX腹膜内连续20天处理三组5只4-6周龄雌性Balb/c荷瘤小鼠（小鼠乳腺肿瘤）。使用数字游标卡尺测量肿瘤体积（精确度为0.01）。将小鼠处死，并使用流式细胞术（BD，USA）获得肿瘤浸润TcB的百分比。结果：我们的结果表明，ART可以减少肿瘤间质（P值= 0.05）和对照组中的T细胞数量。此外，ART增加了脾细胞培养物中产生的IFN γ/IL-4比率（P值= 0.05）。Treg细胞在肿瘤组织中的早期积累与肿瘤进展相关，并且是不良预后的指示。根据所得结果，ART可以减少TBER的数量。我们建议使用具有双重作用机制的青蒿素。它可以有效地杀死癌细胞沿着减少抑制性微环境。(C)2010爱思唯尔有限公司版权所有。
Background: Artemisinin (ART) is a sesquiterpene lactone. Possessing an endoperoxide bridge is unique among ant-imalarial drugs, and now much attention is focused on the anti-cancer properties of ART. In this study we aimed at the immunomodulatory effects of artemisinin in the treatment of breast cancer in comparison to the conventional anti-cancer drug, cyclophasphamide (CTX).Methods: We examined delayed-type hypersensitivity, antibody and IL-4 and IFN gamma production, tumour volume, tumour infiltrated regulatory T cells (Treg) and spleen lymphocyte proliferation assay. Briefly three groups of five 4-6 week old female Balb/c tumour-bearing mice (mouse mammary tumour) were treated with 2.8 mg/kg ART and 20 mg/kg CTX intraperitoneally for 20 consecutive days. Tumour volume was measured using a digital vernier calliper (with accuracy of 0.01). Mice were sacrificed and percentage of tumour infiltrating Tregs were obtained using flow cytometry (BD, USA). Proliferation of splenocytes was obtained using BrdU proliferation assay (Roche).Results: Our results showed that ART can reduce the number of Tregs in tumour stroma (P-value = 0.05) and control. Furthermore ART increased IFN gamma/IL-4 ratio produced in splenocyte culture (P-value = 0.05).Discussion: Cancer is a multi-factorial disease which needs a multi-approach treatment. Early accumulation of Treg cells in the tumour tissue correlates with tumour progression and is an indication of bad prognosis. According to the obtained results, ART can reduce the number of Tregs. We suggest using artemisinin, with its dual action mechanism. It can effectively kill cancer cells along with reducing the suppressive microenvironment. (C) 2010 Elsevier B.V. All rights reserved.