Acquisition of drug resistance by constitutive suppression of NF-κB in ras-transformed NIH3T3 mouse fibroblasts

  • Authors:
    • Tsukasa Sakaida
    • Yasuo Iwadate
    • Sachi Yamaji
    • Masae Uehara
    • Asao Noda
    • Masaki Takiguchi
    • Akira Yamaura
    • Takaki Hiwasa
  • View Affiliations

  • 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.

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October 2003
Volume 23 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sakaida T, Iwadate Y, Yamaji S, Uehara M, Noda A, Takiguchi M, Yamaura A and Hiwasa T: Acquisition of drug resistance by constitutive suppression of NF-κB in ras-transformed NIH3T3 mouse fibroblasts. Int J Oncol 23: 1071-1077, 2003
APA
Sakaida, T., Iwadate, Y., Yamaji, S., Uehara, M., Noda, A., Takiguchi, M. ... Hiwasa, T. (2003). Acquisition of drug resistance by constitutive suppression of NF-κB in ras-transformed NIH3T3 mouse fibroblasts. International Journal of Oncology, 23, 1071-1077. https://doi.org/10.3892/ijo.23.4.1071
MLA
Sakaida, T., Iwadate, Y., Yamaji, S., Uehara, M., Noda, A., Takiguchi, M., Yamaura, A., Hiwasa, T."Acquisition of drug resistance by constitutive suppression of NF-κB in ras-transformed NIH3T3 mouse fibroblasts". International Journal of Oncology 23.4 (2003): 1071-1077.
Chicago
Sakaida, T., Iwadate, Y., Yamaji, S., Uehara, M., Noda, A., Takiguchi, M., Yamaura, A., Hiwasa, T."Acquisition of drug resistance by constitutive suppression of NF-κB in ras-transformed NIH3T3 mouse fibroblasts". International Journal of Oncology 23, no. 4 (2003): 1071-1077. https://doi.org/10.3892/ijo.23.4.1071