NFκB Signaling Related Molecular Alterations in Human Neuroblastoma Cells after Fractionated Irradiation

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概要

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• 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 IκB α 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.

• 2009-07-16

著者

• MADHUSOODHANAN Rakhesh

  Department of Radiation Oncology, University of Oklahoma Health Sciences Center

• NATARAJAN Mohan

  Department of Radiation Oncology, University of Texas Health Sciences Center at San Antonio

• VEERARAGHAVAN Jamunarani

  Department of Radiation Oncology, University of Oklahoma Health Sciences Center

• HERMAN Terence

  Department of Radiation Oncology, University of Oklahoma Health Sciences Center

• JAMGADE Ambarish

  Department of Radiation Oncology, University of Oklahoma Health Sciences Center

• SINGH Nisha

  Department of Radiation Oncology, University of Oklahoma Health Sciences Center

• ARAVINDAN Natarajan

  Department of Radiation Oncology, University of Oklahoma Health Sciences Center

• Singh Nisha

  Department Of Radiation Oncology University Of Oklahoma Health Sciences Center

• Herman Terence

  Department Of Radiation Oncology University Of Oklahoma Health Sciences Center

• Natarajan Mohan

  Department Of Radiation Oncology University Of Texas Health Sciences Center At San Antonio

• Jamgade Ambarish

  Department Of Radiation Oncology University Of Oklahoma Health Sciences Center

• Aravindan Natarajan

  Department Of Radiation Oncology University Of Oklahoma Health Sciences Center

• Madhusoodhanan Rakhesh

  Department Of Radiation Oncology University Of Oklahoma Health Sciences Center

• Veeraraghavan Jamunarani

  Department Of Radiation Oncology University Of Oklahoma Health Sciences Center

• Natarajan Mohan

  Department Of Radiation Oncology The University Of Texas Health Science Center At San Antonio

関連論文

• NFκB Signaling Related Molecular Alterations in Human Neuroblastoma Cells after Fractionated Irradiation
• Endothelial Cell Migration was Impaired by Irradiation-Induced Inhibition of SHP-2 in Radiotherapy : an In vitro Study

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