文章基本信息

标题：NFκB Signaling Related Molecular Alterations in Human Neuroblastoma Cells after Fractionated Irradiation
其他标题：NFκB Signaling Related Molecular Alterations in Human Neuroblastoma Cells after Fractionated Irradiation
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作者：Rakhesh MADHUSOODHANAN ; Mohan NATARAJAN ; Jamunarani VEERARAGHAVAN 等
期刊名称：Journal of Radiation Research
印刷版ISSN：0449-3060
电子版ISSN：1349-9157
出版年度：2009
卷号：50
期号：4
页码：311-324
DOI：10.1269/jrr.08110
摘要：Radiotherapy has been used as an adjunctive local-control modality for high-risk neuroblastoma. However, relapse due to radioresistance affects the success of radiotherapy. Ascertaining the fractionated radiation (FIR) modulated molecular targets is imperative in targeted molecular therapy. Accordingly, we investigated the (i) expression of genes representing six functional pathways; (ii) NFκB DNA-binding activity and (iii) expression of radioresponsive molecules after single dose (10 Gy) radiation (SDR) and FIR (2 Gy × 5) in human neuroblastoma cells. Alterations in gene expression were analyzed using QPCR-profiling, NFκB activity using electrophoretic mobility shift assay (EMSA) and pIκBα using immunoblotting. Modulations in TNFα, IL-1α, pAKT, IAP1, IAP2, XIAP, survivin, MnSOD, BID, Bak, MyD88 and Vegfc were determined using quantitative real-time PCR (Q-PCR) and immunoblotting. Compared to SDR, FIR significantly induced the expression of 25 genes and completely suppressed another 30 genes. Furthermore, FIR induced NFκB-DNA-binding activity and IκBα phosphorylation. Similarly, we observed an induced expression of IAP1, IAP2, XIAP, Survivin, IL-1α, MnSOD, Bid, Bak, MyD88, TNFα and pAKT in cells exposed to FIR. The results of the study clearly show distinct differences in the molecular response of cells between SDR and FIR. We identified several potential targets confining to NFκB signaling cascade that may affect radio-resistance after FIR.
关键词：Radioadaptive response; NFκB; Fractionated irradiation; Neuroblastoma; Transcriptional responses after FIR