Faculty Collaboration Database

Synergistic effect of 15-lipoxygenase 2 and radiation in killing head-and-neck cancer. Cancer Gene Ther 2008 May;15(5):323-30

Date

02/23/2008

Pubmed ID

18292796

DOI

10.1038/cgt.2008.9

Scopus ID

2-s2.0-41949103643 (requires institutional sign-in at Scopus site)   10 Citations

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 muM) but not at low concentrations induced upregulation of its endogenous ligand PPARgamma. 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 PPARgamma dependent.

Author List

Yang Q, Feng Y, Schultz CJ, Li XA, Wu H, Wang D

Authors

Xiaochuan Allen Li PhD Emeritus Professor in the Radiation Oncology department at Medical College of Wisconsin
Christopher J. Schultz MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apoptosis
Arachidonate 15-Lipoxygenase
Cell Line, Tumor
Cell Survival
Combined Modality Therapy
ErbB Receptors
Genes, Reporter
Genetic Vectors
Head and Neck Neoplasms
Humans
Lipoxygenase
Luciferases
Promoter Regions, Genetic