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

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.

• Authors: Fang Tian, Tianli Fan, Yanan Jiang, Xiaoyan Zhang, Xinhua Wang
• Journal: Pathology, research and practice (Pathol Res Pract) Vol. 208 Issue 1 Pg. 32-8 (Jan 15 2012) ISSN: 1618-0631 [Electronic] Germany
• PMID: 22186294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier GmbH. All rights reserved.

Chemical References

• Antineoplastic Agents
• RNA, Small Interfering
• Transcription Factor RelA
• Fluorouracil

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Blotting, Western
• Carcinoma, Squamous Cell (genetics, metabolism)
• Cell Proliferation (drug effects)
• Down-Regulation
• Esophageal Neoplasms (genetics, metabolism)
• Fluorouracil (pharmacology)
• Gene Knockdown Techniques
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Mice
• Mice, Nude
• RNA, Small Interfering
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Transcription Factor RelA (antagonists & inhibitors, genetics, metabolism)
• Xenograft Model Antitumor Assays