Antisense oligonucleotide Elk-1 suppresses the tumorigenicity of human hepatocellular carcinoma cells
Antisense oligonucleotide Elk-1 suppresses the tumorigenicity of human hepatocellular carcinoma cells
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DOI：
10.1016/j.cellbi.2007.08.027
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发表时间：
2008-02-01
影响因子：
3.9
通讯作者：
Liu, Jer-Yuh
中科院分区：
文献类型：
--
作者：
Ying, Tsung-Ho;Hsieh, Yi-Hsien;Liu, Jer-Yuh
在以前的研究中，我们发现，减少Ets样蛋白-1（Elk-1）的表达抑制蛋白激酶C α（PKC α）的表达，并减少细胞迁移和侵袭在人肝细胞癌（HCC）。在这项研究中，我们研究了Elk-1在肿瘤发生中的作用。用ElK-1反义寡核苷酸（ODN）转染SK-Hep-1 HCC细胞。在预处理的细胞中，我们使用RT-PCR检测到mRNA水平的降低。MTT法测定细胞生长抑制率。将预处理的SK-Hep-1肝癌细胞接种于裸鼠皮下，观察肿瘤生长情况，计算抑瘤率。结果显示，5 μ M的反义ODN Elk-1抑制了阳离子脂质体介导转染后SK-Hep-1 HCC细胞的Elk-1和PKC α的产生，分别为对照值的8%和1%，并且在2-5 μ M的反义ODN Elk-1剂量下，SK-Hep-1 HCC细胞的生长受到抑制。对照试剂，正义ODN Elk-1，没有显示出效果。在BALB/裸鼠中，用5 μ M反义ODNElk-1转染的SK-Hep-1HCC细胞形成的肿瘤比正义ODNElk-1预处理的细胞小得多。最大抑瘤率为80.8 ± 12.6%，成瘤时间由13天延长至25天。这些结果表明，反义ODNElk-1作为一种新的试剂，肝癌治疗的有用性。(C)2007年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
In previous studies, we showed that reducing Ets-like protein-1 (Elk-1) expression inhibited protein kinase C alpha (PKC alpha) expression and decreased cell migration and invasion in human hepatocellular carcinoma (HCC). In this study, we have investigated the role of Elk-1 in tumorigenesis. SK-Hep-1 HCC cells were transfected with the ElK-1 antisense oligonucleotide (ODN). In the pretreated cells we detected a reduction of mRNA level using RT-PCR. The inhibitory rate of cell growth was measured by MTT assay. Pretreated-SK-Hep-1 HCC cells were implanted subcutaneously into nude mice to observe the tumor growth and calculate tumor inhibitory rate. The results showed that 5 mu M of the antisense ODN Elk-1 suppressed both Elk-1 and PKC alpha production by SK-Hep-1 HCC cells after cationic liposome-mediated transfection, to 8% and 1% of control values, respectively, and the growth of SK-Hep-1 HCC cells was inhibited at 2-5 mu M doses of the antisense ODN Elk-1. The control reagent, sense ODN Elk-1, showed no effects. In BALB/nude mice, SK-Hep-1 HCC cells transfected with the 5 mu M antisense ODN Elk-1 formed tumors much smaller than those of sense ODN Elk-1 pretreated cells. The maximum inhibitory rate of tumor growth was 80.8 +/- 12.6% and the tumor formation time was prolonged from 13 to 25 days. These findings suggested the usefulness of antisense ODN Elk-1 as a new reagent for liver cancer therapy. (C) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.