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小干扰 RNA 靶向 Krüppel 样因子 8 抑制肾癌细胞 786-0 细胞的体内外生长。

Small interference RNA targeting Krüppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo.

机构信息

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2010 Aug;136(8):1255-65. doi: 10.1007/s00432-010-0776-0. Epub 2010 Feb 25.

DOI:10.1007/s00432-010-0776-0
PMID:20182889
Abstract

PURPOSE

Krüppel-like factor 8 (KLF8) plays an important role in oncogenic transformation and is highly overexpressed in several types of human cancer. We investigated the expression of KLF8 in renal cell carcinoma (RCC) tissues and the role of small interference RNA targeting KLF8 on growth, cell cycle, and apoptosis of human renal carcinoma cell line 786-0 in vitro and in vivo.

METHODS

The expression of KLF8 protein and mRNA in human renal carcinoma samples was detected by immunochemistry and reverse transcription polymerase chain reaction (RT-PCR). The effects of small interference RNA (siRNA) targeting KLF8 on growth, invasiveness, cell cycle, and apoptosis of 786-0 cells were evaluated by MTT assay, Matrigel Invasion Assay, and flow cytometry in vitro. We also investigated effect of siRNA targeting KLF8 on growth of 786-0 cells in nude mice in vivo.

RESULTS

Immunohistochemistry and RT-PCR results showed the expression of KLF8 protein and mRNA in RCC specimens was significantly higher than that in the adjacent non-tumorous renal tissues (P < 0.001). KLF8-siRNA depressed the cellular growth and invasion of 786-0 cells in vitro. The flow cytometry results revealed that KLF8-siRNA could induce an increase in G0/G1 phase cells and induce cell apoptosis. Intratumor injection of siRNA targeting KLF8 inhibited the growth of 786-0 cells in vivo in nude mice tumor model.

CONCLUSIONS

KLF8 possibly involved in regulating the cell growth, invasion, apoptosis, and proliferation of renal carcinoma cancer cells. Blocking the KLF8 channel might be a potential therapeutic strategy for RCC.

摘要

目的

Krüppel 样因子 8(KLF8)在致癌转化中发挥重要作用,在多种人类癌症中高度过表达。我们研究了 KLF8 在肾细胞癌(RCC)组织中的表达,以及针对 KLF8 的小干扰 RNA(siRNA)对体外和体内人肾癌细胞系 786-0 生长、细胞周期和凋亡的作用。

方法

通过免疫化学和逆转录聚合酶链反应(RT-PCR)检测人肾癌样本中 KLF8 蛋白和 mRNA 的表达。通过 MTT 测定、Matrigel 侵袭测定和流式细胞术评估针对 KLF8 的 siRNA 对 786-0 细胞生长、侵袭、细胞周期和凋亡的影响。我们还研究了针对 KLF8 的 siRNA 对体内裸鼠 786-0 细胞生长的影响。

结果

免疫组化和 RT-PCR 结果显示,RCC 标本中 KLF8 蛋白和 mRNA 的表达明显高于相邻非肿瘤性肾组织(P < 0.001)。KLF8-siRNA 抑制了 786-0 细胞在体外的细胞生长和侵袭。流式细胞术结果表明,KLF8-siRNA 可诱导 G0/G1 期细胞增加并诱导细胞凋亡。肿瘤内注射针对 KLF8 的 siRNA 抑制了裸鼠肿瘤模型中 786-0 细胞的体内生长。

结论

KLF8 可能参与调节肾癌细胞的细胞生长、侵袭、凋亡和增殖。阻断 KLF8 通道可能是治疗 RCC 的一种潜在治疗策略。

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