Gene expression analysis of cell death induction by taurolidine in different malignant cell lines.
Gene expression analysis of cell death induction by taurolidine in different malignant cell lines.
复制标题
DOI：
10.1186/1471-2407-10-595
复制
发表时间：
2010-10-30
期刊：
影响因子：
3.8
通讯作者：
Uhl W
中科院分区：
文献类型：
--
作者：
Chromik AM;Hahn SA;Daigeler A;Flier A;Bulut D;May C;Harati K;Roschinsky J;Sülberg D;Weyhe D;Mittelkötter U;Uhl W
抗感染剂牛磺罗定 (TRD) 已被证明具有诱导细胞死亡的特性，但其作用机制尚不清楚。本研究的目的是确定在源自不同癌症类型的肿瘤细胞系中 TRD 治疗后在转录水平上调节的潜在共同靶基因。将五种不同的恶性细胞系（HT29、Chang Liver、HT1080、AsPC-1 和 BxPC-3）与 TRD（100 μM、250 μM 和 1000 μM）一起孵育。分别通过BrdU测定和FACS分析来分析8小时后的增殖和24小时后的细胞活力。使用安捷伦微阵列平台进行基因表达分析，以鉴定在所有细胞系中添加 TRD 后表现出联合调控的基因。对候选基因进行 Ingenuity Pathways 分析，并通过 qRT-PCR 和 Western Blot 验证所选基因。 TRD 250 μM 可显着抑制所有细胞系的增殖以及凋亡细胞死亡。在基因表达调节最强的细胞死亡相关基因中，我们鉴定了促凋亡转录因子（EGR1、ATF3）以及参与内质网应激反应（PPP1R15A）、泛素化（TRAF6）和线粒体凋亡途径（PMAIP1）的基因。这是首次在不同恶性细胞系中同时进行的 TRD 潜在靶基因联合分析。结果表明TRD可能参与导致细胞凋亡的不同信号转导途径。
The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types. Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 μM, 250 μM and 1000 μM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent -microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot. TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1). This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis.
登录
查看更多内容
影响因子：
2.2
作者：
Braumann, Chris;Jacobi, Christoph A.;Hofmann, Maja
通讯作者：
Hofmann, Maja
影响因子：
8.4
作者：
Cho, Kyou-Nam;Sukhthankar, Mugdha;Baek, Seung Joon
通讯作者：
Baek, Seung Joon
DOI：
10.1186/1756-9966-27-82
发表时间：
2008-12-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Daigeler A;Brenzel C;Bulut D;Geisler A;Hilgert C;Lehnhardt M;Steinau HU;Flier A;Steinstraesser L;Klein-Hitpass L;Mittelkötter U;Uhl W;Chromik AM
通讯作者：
Chromik AM
影响因子：
4.8
作者：
Allen-Jennings, AE;Hartman, MG;Hai, T
通讯作者：
Hai, T
影响因子：
5.3
作者：
Jiang, HY;Wek, SA;Wek, RC
通讯作者：
Wek, RC