Department of Pathophysiology, School of Basic Medicine, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Pathol Res Pract. 2012 Jan 15;208(1):32-8. doi: 10.1016/j.prp.2011.10.011. Epub 2011 Dec 18.
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.
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。
