Chronic hypoxia protects against γ-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein

  • Authors:
    • Olivier Cuisnier
    • Raphael Serduc
    • Jean-Pierre Lavieille
    • Michel Longuet
    • Emile Reyt
    • Catherine Riva
  • View Affiliations

  • Published online on: October 1, 2003     https://doi.org/10.3892/ijo.23.4.1033
  • Pages: 1033-1041
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Abstract

Malignant tumours contain zones of chronic or acute hypoxia, which influence their prognosis and progression. The goal of our study was to understand the role of hypoxia in radio-resistance in a squamous cell carcinoma cell line of the head and neck (KB-3-1 cells). Cell growth was evaluated by Trypan blue exclusion under chronic hypoxia (3-5% O2) for 4 weeks or under normal conditions (21% O2). Cells were then γ-irradiated either by X-ray (2-6 Gy) or UV-C radiation (0.001-10 J/cm2). Apoptosis was estimated by double staining with orange acridine and ethydium bromide and fluorescence microscopy. DNA content was estimated by FACS analysis. Expression of Bax, Bcl-2 and P53 was assessed by immunofluorescence and Western blotting. ROS production was measured by dichlorofluorescein fluorescence. Cell growth depends on oxygen tension. It decreased by 42 and 70% at 5 and 3% O2 compared to control with a significant cell cycle arrest rather than increased mortality. Hypoxic cells are more radio-resistant (x2.5) than normoxic cells. Under chronic hypoxia, Bcl-2 increased considerably in cells compared to control, while Bax and P53 did not change. After irradiation, in hypoxic cells very weak expression of the pro-apoptotic Bax protein and no translocation of Bax to the mitochondria were observed. In addition, irradiation of control KB-3-1 cells demonstrated a large increase in ROS production (x2) compared to cells irradiated identically under hypoxia. In conclusion, chronic hypoxia: i) seems to slow-down cell growth of KB-3-1 cells without inducing apoptosis, ii) induces Bcl-2 overexpression and prevents radiation-induced apoptosis by inhibiting ROS production and altering Bax subcellular redistribution and conformational changes.

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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
Cuisnier O, Serduc R, Lavieille J, Longuet M, Reyt E and Riva C: Chronic hypoxia protects against γ-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein. Int J Oncol 23: 1033-1041, 2003
APA
Cuisnier, O., Serduc, R., Lavieille, J., Longuet, M., Reyt, E., & Riva, C. (2003). Chronic hypoxia protects against γ-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein. International Journal of Oncology, 23, 1033-1041. https://doi.org/10.3892/ijo.23.4.1033
MLA
Cuisnier, O., Serduc, R., Lavieille, J., Longuet, M., Reyt, E., Riva, C."Chronic hypoxia protects against γ-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein". International Journal of Oncology 23.4 (2003): 1033-1041.
Chicago
Cuisnier, O., Serduc, R., Lavieille, J., Longuet, M., Reyt, E., Riva, C."Chronic hypoxia protects against γ-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein". International Journal of Oncology 23, no. 4 (2003): 1033-1041. https://doi.org/10.3892/ijo.23.4.1033