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Synergistic effect of 15-lipoxygenase 2 and radiation in killing head-and-neck cancer

Cancer Gene Therapy volume 15, pages 323–330 (2008)Cite this article

Abstract

We previously demonstrated that 15-LOX-2 is significantly reduced in head and neck carcinoma and restoration of 15-LOX-2 expression results in tumor inhibition in HNC. The aim of this study is to evaluate 15-LOX-2 as a candidate for targeted radiotherapy. Molecular subcloning was performed to create a radiation-inducible 15-LOX-2 expression vector in which the full-length 15-LOX-2 cDNA was inserted downstream the recombinant Egr-1 promoter. The radiation-induced downregulations of 15-LOX-2 protein (twofold up) and its main metabolite 15S-HETE (threefold up) were observed in HNC cells transfected with the 15-LOX-2 expression vector after 4 Gy of radiation. Radiation-induced upregulation of 15-LOX-2 resulted in significant induction of apoptosis in HNC cells. Furthermore, survival colony formation was significantly reduced by 4 Gy in the HNC cells containing the 15-LOX-2 expression vector compared with the controls. Radiation-induced upregulation of 15-LOX-2 results in significant induction of apoptosis and enhances killing effect of radiotherapy in HNC. In addition, exogenous addition of 15S-HETE at high concentrations (⩾10 μM) but not at low concentrations induced upregulation of its endogenous ligand PPARγ. In conclusion, synergistic effect between radiation and 15-LOX-2 was observed in killing HNC. 15-LOX-2 may be a potential target in radiation-targeted therapy of HNC. The 15-LOX-2 inhibition may not be PPARγ dependent.

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Abbreviations

15-LOX-2:

15-lipoxygenase 2

15S-HETE:

15S- hydroxyeicosatetraenoic acid

AA:

arachidonic acid

Egr-1:

early growth response 1 gene

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

HNC:

head-and-neck cancer

PPARγ:

peroxisome proliferators-activated receptor γ

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Authors and Affiliations

  1. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Q Yang, Y Feng, C J Schultz, X A Li & D Wang

  2. Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin, Milwaukee, WI, USA

    H Wu

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  1. Q Yang
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Correspondence to D Wang.

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Yang, Q., Feng, Y., Schultz, C. et al. Synergistic effect of 15-lipoxygenase 2 and radiation in killing head-and-neck cancer. Cancer Gene Ther 15, 323–330 (2008). https://doi.org/10.1038/cgt.2008.9

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