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替瑞诺醇分子调节免疫应答,减少调节性 T 细胞,并抑制体内肿瘤生长。

Tehranolide molecule modulates the immune response, reduce regulatory T cell and inhibits tumor growth in vivo.

机构信息

Department of Biochemistry, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Mol Immunol. 2010 Apr;47(7-8):1579-84. doi: 10.1016/j.molimm.2010.01.007. Epub 2010 Feb 9.

DOI:10.1016/j.molimm.2010.01.007
PMID:20138670
Abstract

Tehranolide named as new type of a sesquiterpene lactone with an endoperoxide group which purified from Artemisia diffusa and having similar structure to Artemisinin. Tehranolide is hypothesized to possess effects akin to Artemisinin, which is active against cancer cells. In the present research we emphasized on the direct correlation between the tumor sizes, immune response; including cytokin network, T regulatory cells and Tehranolide intraperitoneally injected Tehranolide. In this study, Tehranolide was purified from Artemisia difussa. First we evaluated the effects of Tehranolide on cell growth inhibition (in vitro) by MTT assay and second investigated the immune responses, these include measuring tumor growth in the female Balb/c mice transplanted with spontaneous mouse mammary tumor and treated with Tehranolide, splenocyte proliferation detected by using the BrdU kit, measurement of cytokine profile by ELISA and analysis of T-lymphocytes subpopulation in spleen by Flow cytometry. Our results showed a significant (p<0.05) decrease in the tumor volume and the level of IL-4 in the animals treated with Tehranolide, compared to untreated group. In addition, a significant (p<0.05) increase in the lymphocytes proliferation and the level of IFN-gamma in the animals treated with Tehranolide in comparison with control group. Furthermore, we regulate the regulatory T cells in order to improve the outcome of cancer immunotherapy. The measurement of splenic CD4(+)CD25(+)Foxp3(+) T lymphocytes indicated that Tehranolide significantly (p<0.05) decreased the number of these lymphocytes. These findings show that the use of Tehranolide molecule represents a novel strategy with major suggestions for cancer therapy approaches.

摘要

特汉隆内酯被命名为一种新型倍半萜内酯,具有内过氧化物基团,从艾蒿中分离得到,其结构与青蒿素相似。特汉隆内酯被假设具有与青蒿素相似的作用,对癌细胞具有活性。在本研究中,我们强调了肿瘤大小、免疫反应之间的直接相关性,包括细胞因子网络、T 调节细胞和腹腔内注射特汉隆内酯。在这项研究中,特汉隆内酯从艾蒿中分离得到。首先,我们通过 MTT 测定评估了特汉隆内酯对细胞生长抑制(体外)的影响,其次研究了免疫反应,包括测量用特汉隆内酯治疗的自发性小鼠乳腺肿瘤移植的雌性 Balb/c 小鼠的肿瘤生长、用 BrdU 试剂盒检测脾细胞增殖、用 ELISA 测量细胞因子谱以及用流式细胞术分析脾 T 淋巴细胞亚群。我们的结果表明,与未治疗组相比,用特汉隆内酯治疗的动物的肿瘤体积和 IL-4 水平显著(p<0.05)降低。此外,与对照组相比,用特汉隆内酯治疗的动物的淋巴细胞增殖和 IFN-γ水平显著(p<0.05)增加。此外,我们调节调节性 T 细胞以改善癌症免疫治疗的结果。脾 CD4(+)CD25(+)Foxp3(+)T 淋巴细胞的测量表明,特汉隆内酯显著(p<0.05)降低了这些淋巴细胞的数量。这些发现表明,使用特汉隆内酯分子代表了一种新的策略,对癌症治疗方法有重要的建议。

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