TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma.
TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma.
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DOI：
10.1186/1756-9966-27-82
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发表时间：
2008-12-12
期刊：
影响因子：
--
通讯作者：
Chromik AM
中科院分区：
文献类型：
--
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
由于缺乏有效的细胞抑制剂，播散性软组织肉瘤仍然是一个治疗困境。因此，我们测试了 TRAIL 和 Tarolidine (TRD) 这两种对人纤维肉瘤 (HT1080) 具有凋亡特性的物质。通过 TUNEL 分析观察活力、细胞凋亡和坏死，并通过 FACS 分析（碘化丙啶/AnnexinV 染色）进行定量。通过 RNA 微阵列分析基因表达，并通过 rtPCR 验证所选基因的结果。通过蛋白质印迹分析记录蛋白质水平的变化。通过 ELISA 分析 NFKB 活性并进行增殖测定 (BrdU)。单一物质 TRAIL 和 TRD 诱导 HT1080 细胞凋亡并显着降低增殖。与凋亡途径相关的几个基因（TRAIL：ARHGDIA、NFKBIA、TNFAIP3；TRD：HSPA1A/B、NFKBIA、GADD45A、SGK、JUN、MAP3K14）的基因表达发生变化。与单一物质相比，TRD 和 TRAIL 的组合显着增加了细胞凋亡，并导致多种基因（HSPA1A/B、NFKBIA、PPP1R15A、GADD45A、AXL、SGK、DUSP1、JUN、IRF1、MYC、BAG5、BIRC3）的表达变化。 NFKB 活性测定揭示了与单独的 TRAIL 相比，TRD 和 TRD+TRAIL 对 NFKB 的几个亚基的反足调节。 TRD 和 TRAIL 可有效诱导人纤维肉瘤细胞凋亡并减少增殖。多种基因似乎都参与其中，表明 NFKB 通路是 TRD/TRAIL 介导的细胞凋亡的关键调节因子。
Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD), two substances with apoptogenic properties on human fibrosarcoma (HT1080). Viability, apoptosis and necrosis were visualized by TUNEL-Assay and quantitated by FACS analysis (Propidiumiodide/AnnexinV staining). Gene expression was analysed by RNA-Microarray and the results validated for selected genes by rtPCR. Protein level changes were documented by Western Blot analysis. NFKB activity was analysed by ELISA and proliferation assays (BrdU) were performed. The single substances TRAIL and TRD induced apoptotic cell death and decreased proliferation in HT1080 cells significantly. Gene expression of several genes related to apoptotic pathways (TRAIL: ARHGDIA, NFKBIA, TNFAIP3; TRD: HSPA1A/B, NFKBIA, GADD45A, SGK, JUN, MAP3K14) was changed. The combination of TRD and TRAIL significantly increased apoptotic cell death compared to the single substances and lead to expression changes in a variety of genes (HSPA1A/B, NFKBIA, PPP1R15A, GADD45A, AXL, SGK, DUSP1, JUN, IRF1, MYC, BAG5, BIRC3). NFKB activity assay revealed an antipodal regulation of the several subunits of NFKB by TRD and TRD+TRAIL compared to TRAIL alone. TRD and TRAIL are effective to induce apoptosis and decrease proliferation in human fibrosarcoma. A variety of genes seems to be involved, pointing to the NFKB pathway as key regulator in TRD/TRAIL-mediated apoptosis.
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影响因子：
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作者：
Clevenger, CV;Thickman, K;Reed, JC
通讯作者：
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