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蒿甲醚在体内发挥抗肿瘤活性并减少CD4+CD25+FOXP3+调节性T细胞。

Arteether exerts antitumor activity and reduces CD4+CD25+FOXP3+ T-reg cells in vivo.

作者信息

Azimi Mohamadabadi Maryam, Hassan Zuhair Mohammad, Zavaran Hosseini Ahmad, Gholamzad Mehrdad, Noori Shekoofe, Mahdavi Mehdi, Maroof Hamidreza

机构信息

Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran, e-mail:

出版信息

Iran J Immunol. 2013 Sep;10(3):139-49.

PMID:24076591
Abstract

BACKGROUND

Chemo-immunotherapy is one of the new achievements for treatment of cancer, by which the success of anti-cancer therapy can be increased. In vitro studies have been shown that Arteether (ARE) induces apoptosis in tumor cells, but not in normal cells.

OBJECTIVE

To investigate the cytotoxic and immunomodulatory properties of Arteether in-vivo and in-vitro.

METHODS

In this study, we used MTT assay for evaluation of cytotoxicity of Arteether on tumor cell line and Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals. Balb/c mice were subcutaneously transplanted with tumor tissue taken from Spontaneous Mouse Mammary Tumor (SMMT) bearing female mice. Arteether was administered to breast tumor-bearing Balb/c mice at a dose of 6mg/kg/day intraperitoneally. Tumor sizes, lymphocyte proliferation, cytokines production, and the percentage of splenic T-reg cells were measured.

RESULTS

We observed that ARE could reduce the cell growth of 4T1 cell line in a dose-dependent manner but it had no cytotoxic effect on the growth of peripheral blood lymphocytes. ARE administered intraperitoneally to tumor-bearing Balb/c mice could reduce the tumor growth rate and splenic T-reg cells. No difference in the IFN-γ, IL-10 and IL-4 production was observed between tumor antigen-stimulated splenocytes of mice treated with ARE and control mice.

CONCLUSION

These results underscore antitumor properties of Arteether that may aid in development of more effective antitumor agents.

摘要

背景

化学免疫疗法是癌症治疗的新成果之一,通过该疗法可提高抗癌治疗的成功率。体外研究表明,蒿甲醚(ARE)可诱导肿瘤细胞凋亡,但对正常细胞无此作用。

目的

研究蒿甲醚在体内和体外的细胞毒性及免疫调节特性。

方法

在本研究中,我们使用MTT法评估蒿甲醚对肿瘤细胞系和健康个体外周血单个核细胞(PBMCs)的细胞毒性。将取自患有自发性小鼠乳腺肿瘤(SMMT)的雌性小鼠的肿瘤组织皮下移植到Balb/c小鼠体内。以6mg/kg/天的剂量腹腔注射蒿甲醚给荷乳腺肿瘤的Balb/c小鼠。测量肿瘤大小、淋巴细胞增殖、细胞因子产生以及脾调节性T细胞的百分比。

结果

我们观察到ARE能以剂量依赖性方式降低4T1细胞系的细胞生长,但对外周血淋巴细胞的生长无细胞毒性作用。对荷瘤Balb/c小鼠腹腔注射ARE可降低肿瘤生长速率和脾调节性T细胞。在用ARE处理的小鼠和对照小鼠的肿瘤抗原刺激的脾细胞之间,未观察到IFN-γ、IL-10和IL-4产生的差异。

结论

这些结果强调了蒿甲醚的抗肿瘤特性,这可能有助于开发更有效的抗肿瘤药物。

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