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小干扰 RNA 单独靶向 NF-κB p65 或与 5-FU 联合抑制裸鼠食管鳞癌细胞生长。

A small interfering RNA targeting NF-κB p65 alone or combined with 5-FU inhibits growth of esophageal squamous cell carcinoma in nude mice.

机构信息

Department of Pathophysiology, School of Basic Medicine, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.

出版信息

Pathol Res Pract. 2012 Jan 15;208(1):32-8. doi: 10.1016/j.prp.2011.10.011. Epub 2011 Dec 18.

Abstract

NF-κB signaling pathway plays an important role in carcinogenesis. Although constitutive NF-κB activation has been reported in many human tumors, the effect of NF-κB signaling pathway in esophageal squamous cell carcinoma (ESCC) is still poorly understood. To explore the role of NF-κB signaling pathway in ESCC, RNA interference (RNAi) was used to knockdown the NF-κB p65 protein level in the ESCC cells and nude mice. 5-FU was used to investigate whether knockdown NF-κB p65 can potentiate 5-FU's antitumor effect. Animal results indicated that tumor growth was inhibited in p65 siRNA and p65 siRNA+5-FU groups as compared with the control group. Immunohistochemistry, RT-PCR and TUNEL assay showed that p65 siRNA downregulated the expression of p65 and enhanced the sensitivity of EC9706 cells to 5-FU treatment in vivo. Overall, our work indicates that downregulation of p65 can increase tumor apoptosis and potentiates the effects of 5-FU by suppressing NF-κB signaling pathway. Thus, p65 is an interesting target for ESCC treatment.

摘要

NF-κB 信号通路在肿瘤发生中起着重要作用。尽管在许多人类肿瘤中已经报道了组成性 NF-κB 激活,但 NF-κB 信号通路在食管鳞状细胞癌 (ESCC) 中的作用仍知之甚少。为了探讨 NF-κB 信号通路在 ESCC 中的作用,我们使用 RNA 干扰 (RNAi) 技术敲低 ESCC 细胞和裸鼠中的 NF-κB p65 蛋白水平。使用 5-FU 来研究敲低 NF-κB p65 是否可以增强 5-FU 的抗肿瘤作用。动物实验结果表明,与对照组相比,p65 siRNA 和 p65 siRNA+5-FU 组的肿瘤生长受到抑制。免疫组化、RT-PCR 和 TUNEL 检测结果表明,p65 siRNA 下调了 p65 的表达,并增强了 p65 siRNA 体内对 5-FU 处理的敏感性。总的来说,我们的工作表明,下调 p65 可以通过抑制 NF-κB 信号通路增加肿瘤细胞凋亡,并增强 5-FU 的作用。因此,p65 是 ESCC 治疗的一个有趣的靶点。

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