title: 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.affiliation: Department of Pathophysiology, School of Basic Medicine, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Tianli
authors.initials: T
authors.lastname: Fan
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D005472:Fluorouracil