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Constitutive NF-κB activity influences basal apoptosis and radiosensitivity of head-and-neck carcinoma cell lines

par Didelot, Céline ;Barberi-Heyob, Muriel;Mirjolet, Jean François;Merlin, Jean Louis;Bianchi, Arnaud;Becuwe, Philippe;Dauça, Michel
Référence International journal of radiation oncology, biology, physics, 51, 5, page (1354-1360)
Publication Publié, 2001-12

Article révisé par les pairs

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Résumé :

Purpose: Nuclear factor-κB (NF-κB) has been implicated in anti-apoptotic gene transactivation, according to its transcriptional activity. The present study was designed to investigate whether constitutive NF-κB activity could modulate basal apoptosis and intrinsic radiosensitivity of KB head-and-neck carcinoma cell line and KB3 subline. The KB3 subline was more radiosensitive (SF2 = 0.48, α = 0.064) than the radioresistant KB parental cell line (SF2 = 0.80, α = 0.114). Methods and Materials: Constitutive NF-κB DNA-binding activity was determined using electrophoretic mobility shift assay. Modulation of NF-κB activity was performed by exposing both cell lines to tumor necrosis factor α or dexamethasone. Apoptotic cell population was analyzed using flow cytometry (annexin V/propidium iodide). Radiosensitivity was assessed from determination of the surviving fraction at 2 Gy (SF2), and α and β parameters were determined using the linear-quadratic model. Results: Constitutive NF-κB activity was found to be significantly lower in KB3 than in KB. KB cell line exposure to dexamethasone significantly decreased NF-κB DNA-binding activity and, consequently, enhanced baseline apoptosis and radiosensitivity (α values: 0.114 vs. 0.052). Conversely, exposure of KB3 cells to tumor necrosis factor α increased NF-κB DNA-binding activity and resulted in a significant decrease (50%) in rate of apoptosis and in radiosensitivity (SF2 values: 0.48 vs. 0.63). Conclusions: Modulation of NF-κB DNA-binding activity influences baseline apoptosis and intrinsic radiosensitivity. © 2001 Elsevier Science Inc.