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

Small interference RNA targeting Kruppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo
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DOI:
10.1007/s00432-010-0776-0
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发表时间:
2010-08-01
影响因子:
3.6
通讯作者:
Zhu, Hong-Guang
Zhu, Hong-Guang
中科院分区:
医学3区
文献类型:
--
作者:
Fu, Wei-Jin;Li, Jia-Chu;Zhu, Hong-Guang

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目的Kruppel样因子8(KLF 8)在肿瘤转化中起重要作用,并在多种人类肿瘤中高度表达。方法采用免疫组化和逆转录聚合酶链反应(RT-PCR)方法检测KLF 8蛋白和mRNA在肾癌组织中的表达,并观察小干扰RNA(siRNA)对肾癌细胞株786-0生长、细胞周期和凋亡的影响。采用MTT法、Matrigel侵袭实验和流式细胞术检测KLF 8小干扰RNA(siRNA)对786-0细胞生长、侵袭能力、细胞周期和凋亡的影响。结果免疫组化和RT-PCR结果显示肾细胞癌组织中KLF 8蛋白和mRNA的表达均明显高于癌旁肾组织(P < 0.001); KLF 8-siRNA抑制786-0细胞的生长和侵袭。流式细胞仪检测结果显示,KLF 8-siRNA能诱导G 0/G1期细胞增多,并诱导细胞凋亡。结论KLF 8可能参与了肾癌细胞的生长、侵袭、凋亡和增殖的调控。阻断KLF 8通道可能是治疗肾细胞癌的一个潜在策略。
Purpose Kruppel-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.