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宝藿苷-1在G(1)-S期转变时抑制活化T细胞增殖。

Baohuoside-1 inhibits activated T cell proliferation at G(1)-S phase transition.

作者信息

Ma Anlun, Qi Shijie, Xu Dasheng, Daloze Pierre, Chen Huifang

机构信息

Laboratory of Experimental Surgery, Centre de recherche du CHUM, Hôpital Notre-Dame, Université de Montréal, Montreal, Quebec, Canada H2L 2W5.

出版信息

Transpl Immunol. 2005 Oct;15(1):55-62. doi: 10.1016/j.trim.2005.05.002. Epub 2005 Jun 16.

DOI:10.1016/j.trim.2005.05.002
PMID:16223673
Abstract

BACKGROUND

The effect of baohuoside-1 (B1), a novel flavonoid, on cell proliferation and the cell cycle was evaluated in this study.

METHODS

The antiproliferative properties of B1 were evaluated by proliferation assay. Western blotting and flow cytometric analysis were employed to investigate the expression of cyclins and cyclin-dependent kinase proteins.

RESULTS

The major findings were (1) B1 effectively inhibited the cell proliferation activated by mitogenic antigen, with a 50% inhibitory concentration in low muM and in a dose- and time-dependent manner. (2) B1 resulted in G(1)-S phase cells arrest. (3) It down-regulated the expression of cyclin A, D and p33 cyclin-dependent kinase-2 (p33cdk2) proteins. (4) B1 suppressed the growth of several tumor cell lines. (5) B1 prevented rat heart allograft rejection in vivo.

CONCLUSIONS

B1 immunosuppression of mitogen-activated T cell proliferation occurs in G(1)-S transition. It may be associated with the expression of cyclin A, D and p33cdk2 proteins. B1 prevents rat heart allograft rejection in vivo. The mechanism of B1 is different from tacrolimus and sirolimus.

摘要

背景

本研究评估了新型黄酮类化合物宝藿苷 -1(B1)对细胞增殖和细胞周期的影响。

方法

通过增殖试验评估B1的抗增殖特性。采用蛋白质印迹法和流式细胞术分析来研究细胞周期蛋白和细胞周期蛋白依赖性激酶蛋白的表达。

结果

主要研究结果如下:(1)B1有效抑制有丝分裂原激活的细胞增殖,其半数抑制浓度处于低微摩尔水平,且呈剂量和时间依赖性。(2)B1导致G1期到S期细胞停滞。(3)它下调细胞周期蛋白A、D和p33细胞周期蛋白依赖性激酶2(p33cdk2)蛋白的表达。(4)B1抑制多种肿瘤细胞系的生长。(5)B1在体内可预防大鼠心脏同种异体移植排斥反应。

结论

B1对有丝分裂原激活的T细胞增殖的免疫抑制作用发生在G1期到S期的转变过程中。这可能与细胞周期蛋白A、D和p33cdk2蛋白的表达有关。B1在体内可预防大鼠心脏同种异体移植排斥反应。B1的作用机制不同于他克莫司和西罗莫司。

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