Acquisition of drug resistance by constitutive suppression of NF-κB in ras-transformed NIH3T3 mouse fibroblasts
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- Published online on: October 1, 2003 https://doi.org/10.3892/ijo.23.4.1071
- Pages: 1071-1077
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Abstract
Apoptotic cell death is frequently suppressed by NF-κB transcription factor. We examined the effects of NF-κB on the sensitivity to anti-cancer drugs by using two NF-κB-inhibitory molecules, IκBα-super-repressor (IκBα-SR) and dominant negative IKKβ (IKKβ-DN). Ha-ras-transformed NIH3T3 (ras-NIH3T3) mouse fibroblasts were stably transfected with these cDNAs, and suppression of NF-κB activity was confirmed by electrophoretic mobility shift assays. Cell viability analysis revealed that IκBα-SR- or IKKβ-DN-transfected cells were more resistant to peplomycin, mitomycin C, and camptothecin. Flow cytometric analysis indicated partial G1 arrest of these transfected cells. Consistently, elevated expression of IκBα-SR and IKKβ-DN was accompanied by increased levels of p21 but not of Bax. Transfection of p21 into ras-NIH3T3 cells caused similar reduced chemosensitivity to the anti-cancer drugs. These results collectively indicate that constitutive suppression of NF-κB activity reduced the chemosensitivity to anti-cancer drugs via enhanced expression of p21.